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The Journal of Immunology, 1998, 161: 5627-5632.
Copyright © 1998 by The American Association of Immunologists

Staphylococcal Enterotoxin A-Induced Injury of Human Lung Endothelial Cells and IL-8 Accumulation Are Mediated by TNF-{alpha}1

Nobumitsu Fujisawa*, Shinichiro Hayashi{dagger}, Anna Kurdowska*, James M. Noble*, Keiko Naitoh{dagger} and Edmund J. Miller2,*

* Department of Biochemistry, University of Texas Health Center, Tyler, TX 75710; and {dagger} Department of Medicine, Saga Medical School, Saga, Japan


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Staphylococcal enterotoxin A (SEA), a superantigen produced by some strains of Staphylococcus aureus, causes a variety of clinical manifestations ranging from food poisoning to shock. S. aureus can also be associated with the development of acute respiratory distress syndrome, and SEA has been shown to cause an inflammatory reaction in the lung. Therefore, we examined possible interactions between SEA, PBMCs, polymorphonuclear cells (PMNs), and normal human lung microvascular endothelial cells (HMVEC-L), as well as the role of these interactions on the secretion of IL-8. Injury to HMVEC-L, as measured by the release of 51Cr, increased significantly when HMVEC-L were incubated with SEA and PBMCs. IL-8 was secreted by both PBMCs and HMVEC-L. The accumulation of IL-8 in the culture medium of HMVEC-L was increased by SEA in a dose-dependent manner and was directly related to the number of PBMCs present. Although neither anti-human IL-8 nor IL-1 mAb inhibited HMVEC-L cytotoxicity, anti-human TNF-{alpha} mAb inhibited both the cytotoxicity and IL-8 accumulation completely. When HMVEC-L were incubated with supernatants from SEA-treated PBMCs, HMVEC-L cytotoxicity was comparable with HMVEC-L incubated with SEA and PBMCs at the same time. Although high concentrations of purified PMNs induced HMVEC-L lysis in a dose-dependent manner, the effect of PMNs was not changed in the presence of SEA. These findings suggest that TNF-{alpha} secreted by SEA-stimulated PBMCs plays a leading role in HMVEC-L injury.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Acute respiratory distress syndrome (ARDS)3 is an acute deterioration of lung function that occurs in association with severe clinical disorders such as sepsis (1). Although the pathogenesis of ARDS remains unclear, the interaction between polymorphonuclear cells (PMNs), their toxic products such as myeloperoxidase, and cytokines derived from PBMCs and pulmonary endothelium are thought to increase microvascular permeability to plasma proteins. The resultant lung edema is considered a major component of ARDS (2, 3, 4). Sepsis is one of the clinical disorders that is most often associated with ARDS (5, 6), and many studies have examined the possible role of endotoxin from Gram-negative bacteria, and in particular the cell wall component LPS, in the development of ARDS (7, 8, 9). However, there is a significant group of patients who develop ARDS associated with Gram-positive bacteria such as Staphylococcus aureus which do not produce LPS (10). Staphylococcal enterotoxin A (SEA) is a 28-kDa exoprotein produced by several strains of S. aureus (11). SEA is known to induce TNF-{alpha} and IL-1ß in human monocytic cells (12, 13, 14, 15). Proinflammatory cytokines such as TNF-{alpha} and IL-1ß can stimulate the production of IL-8 (15), and there are reports that describe TNF-{alpha} increasing the permeability of the endothelium (16, 17, 18) and being associated with the acute lung injury (19). IL-8, a potent PMN chemotactic and activating factor, has also been implicated in the pathogenesis of ARDS (20). Furthermore, we have found that IL-8 concentrations are higher in the lungs of patients with ARDS associated with sepsis than in nonseptic ARDS patients (21), and that i.v. SEA increases the IL-8 concentration of plasma and epithelial lining fluid in rabbits (22). In these studies, we examined the mechanism of lung endothelial cell injury associated with SEA.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Human subjects

All work involving human subjects was approved by the Institutional Human Subjects Committee at the University of Texas Health Center.

Cell culture

Human lung microvascular endothelial cells (HMVEC-L) (Clonetics, San Diego, CA) were maintained in EGM medium containing human epidermal growth factor (10 ng/ml), bovine brain extract (12 mg/ml), gentamicin sulfate (50 mg/ml), amphotericin-B (50 ng/ml) (Clonetics), and 10% FCS (Sigma, St. Louis, MO) at 37°C in a humidified atmosphere containing 5% CO2. HMVEC-L were grown as monolayers in tissue culture flasks. Cells were passaged when they reached 70–80% confluence using trypsin (0.025%)/EDTA (0.01%) in HBSS (Clonetics), centrifuged at low speed (220 x g for 5 min), and resuspended in fresh medium. HMVEC-L were maintained for no longer than 3 wk.

Preparation of human PMNs and PBMCs

Human blood from healthy donors was anticoagulated with heparin (Elkins-Sinn, Cherry Hill, NJ). PMNs were isolated by dextran (Pharmacia, Piscataway, NJ) sedimentation and E lysis using the method of Boyum (23) as modified in our earlier studies (24, 25) and were further purified in gradients of Ficoll-Hypaque (density 1.114; ICN Biomedicals, Costa Mesa, CA) (26) for cytotoxic assays. The isolated PMNs were >=99% pure and viable. PBMCs were also isolated in gradients of Ficoll-Hypaque. The isolated PBMCs were >=98% pure and 99% viable.

51Cr release cytotoxicity assay

The assay was performed as described previously (27). In brief, HMVEC-L monolayers in 96-well plates were incubated with 2 Ci/well of Na251CrO4 (DuPont-New England Nuclear, Wilmington, DE) alone or with indicated concentrations of SEA (Toxin Technology, Sarasota, FL) overnight at 37°C. Following the incubation, the wells were washed three times and incubated in culture medium for an additional 30 min at 37°C to allow spontaneous lysis of marginally viable cells. After washing twice, a 100-µl aliquot of SEA, purified mouse IgG1 anti-IL-8 mAb (R&D Systems, Minneapolis, MN), anti-TNF-{alpha} mAb, anti-IL-1ß mAb (Biosource International, Camarillo, CA), freshly isolated PBMCs, and/or PMNs were added to each well. The cells were cultured for 21 h, and the radioactivity in the supernatants was counted using a gamma radiation spectrometer. Each well received culture medium alone or 2% SDS (EM Industries, Cherry Hill, NJ) to determine spontaneous and maximum release, respectively. Percent lysis was calculated using the following formula: % Lysis = ([experimental cpm - spontaneous cpm]/[maximum cpm - spontaneous cpm]) x 100.

Quantitation of IL-8

IL-8 accumulation in the supernatants was quantitated using an ELISA as described previously (28, 29). The assay employed an anti-IL-8 mAb (IgG1) (purified from ascites that had been developed using HB9467 hybridoma cells (American Type Culture Collection, Manassas, VA, with permission from Dr. E. J. Leonard, National Cancer Institute, Frederick, MD)) (28) and rabbit polyclonal anti-human IL-8 polyclonal antiserum (Upstate Biotechnology, Lake Plasid, NY) followed by swine anti-rabbit Igs conjugated with horseradish peroxidase (Dako, Carpinteria, CA). The immunoassay was specific for IL-8 and did not cross-react with other members of the {alpha}-chemokine family (29).

Flow cytometric analysis

Flow cytometric analysis was performed as described previously with some modifications (30). Briefly, PMNs that had been freshly isolated using dextran and Ficoll-Hypaque were incubated with FITC-labeled anti-CD16 mAbs (Exalpha, Boston, MA) for 30 min at 4°C to identify the PMN population. Cells were then washed three times with cold PBS and incubated with phycoerythrin-labeled mAbs for Mac-1 (CD11b; Monosan, Uden, Netherlands) or L-selectin (CD62L; Exalpha) for an additional 30 min at 4°C. Cells were washed again three times and analyzed by FACScan (Becton Dickinson, Mountain View, CA). Control leukocytes were prepared by hypotonic lysis of freshly isolated blood and incubated with mAbs as described above.

Mean fluorescence intensity (MFI) was calculated, and the percent stimulation of expression was calculated using the following formula: % Stimulation = ([MFI of purified PMNs - MFI of control leukocytes]/MFI of control leukocytes) x 100.

Statistics

Data are expressed as mean values ± SD. Significant differences between the means of two groups were assessed using the Student t test. Data were considered statistically significant if p values were <=0.05. The experiments were performed at least twice with at least four replicate cultures per experiment.


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Cytotoxic effect toward HMVEC-L coincubated with SEA, PBMCs, and/or PMNs

Endothelial cell injury was estimated as the release of chromium from prelabeled HMVEC-L. When HMVEC-L were incubated with PBMCs and SEA, HMVEC-L cytotoxicity increased significantly compared with the incubation with PBMCs alone (p < 0.0001) (Fig. 1Go). Alternatively, when HMVEC-L were incubated with PMNs in the presence of SEA, there was no increase in endothelial cell lysis as compared with the incubation with PMNs alone. There was also no additional increase in cytotoxicity when PBMCs and SEA were incubated with PMNs. However, when HMVEC-L and SEA were incubated with PBMCs, the percentage of cell lysis was increased in a dose-dependent manner. There were significant differences from control cultures (incubated without PBMCs) at concentrations >=7.5 x 104 cells/ml of PBMCs (p < 0.007) (Fig. 2GoA). When HMVEC-L and PBMCs were incubated with SEA, the percentage of cell lysis also increased in a dose-dependent manner. There were significant differences from control cultures (incubated without SEA) at concentrations >=0.1 ng/ml of SEA (p < 0.01) (Fig. 2GoB).



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  		FIGURE 1. Cytotoxic effect of SEA, PBMCs, and/or PMNs toward HMVEC-L. HMVEC-L were incubated with PBMCs (1.5 x 105 cells/ml) and/or PMNs (8.5 x 105 cells/ml) in the presence or absence of 10 ng/ml of SEA for 21 h. Next, percent lysis was calculated as described in Materials and Methods.

 


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  		FIGURE 2. Cytotoxic effect of different concentrations of PBMCs and SEA toward HMVEC-L. A, HMVEC-L were incubated with 10 ng/ml of SEA and indicated concentrations of PBMCs for 21 h. B, HMVEC-L were incubated with 1.5 x 105 cells/ml of PBMCs and indicated concentrations of SEA for 21 h.

 
IL-8 accumulation in supernatants of HMVEC-L incubated with SEA, PBMCs, and/or PMNs

SEA contributed to IL-8 production and secretion when it was incubated with PBMCs (Fig. 3Go). When HMVEC-L and PBMCs were incubated with SEA, IL-8 accumulation was increased significantly compared with incubation in the absence of SEA (p = 0.0003). The addition of PMNs did not contribute to the accumulation of IL-8 regardless of the presence of SEA or PBMCs. Interestingly, HMVEC-L produced and secreted IL-8 in the absence of any additional stimuli. When HMVEC-L and SEA were incubated with PBMCs, IL-8 accumulation was increased and was related to the number of PBMCs added; there were significant differences from control cultures (incubated without PBMCs) at concentrations >=1.5 x 104 cells/ml of PBMCs (p < 0.0001) (Fig. 4GoA). When HMVEC-L and PBMCs were coincubated in the presence of SEA, IL-8 accumulation also increased in a dose-dependent manner, and there were significant differences from control cultures (incubated without SEA) at concentrations >=0.001 ng/ml of SEA (p < 0.0001) (Fig. 4GoB).



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  		FIGURE 3. IL-8 accumulation in supernatants of HMVEC-L incubated with PBMCs and/or PMNs in the presence or absence of SEA. HMVEC-L were incubated with PBMCs (1.5 x 105 cells/ml) and/or PMNs (8.5 x 105 cells/ml) in the presence or absence of SEA (10 ng/ml). Supernatants were collected and assayed by ELISA.

 


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  		FIGURE 4. IL-8 accumulation in supernatants of HMVEC-L incubated with PBMCs and SEA. A, HMVEC-L were incubated with 10 ng/ml of SEA and indicated concentrations of PBMCs. B, HMVEC-L were incubated with 1.5 x 105 cells/ml of PBMCs and indicated concentrations of SEA. Supernatants were collected and assayed by ELISA.

 
Effect of supernatants of PBMCs incubated with or without SEA

To determine whether the cytotoxic factor and/or the stimulus for IL-8 production was present in the medium, or whether cell contact was required, PBMCs were incubated for 21 h in the presence or absence of SEA. Next, supernatants were collected and incubated with HMVEC-L. The cytotoxic effects induced by the coincubation of HMVEC-L, PBMCs, and SEA were due to soluble factors released into the medium. When HMVEC-L were incubated with SEA alone (no PBMCs), there was no significant increase in cytotoxicity compared with the incubation with medium alone (Fig. 5GoA). When HMVEC-L were incubated with supernatants that had been incubated with PBMCs in the presence or absence of SEA, the percentage of cell lysis was increased significantly compared with the incubation with medium alone (p < 0.0001 and p = 0.0261, respectively). Furthermore, supernatants from SEA-stimulated PBMCs were equally cytotoxic to HMVEC-L compared with when SEA, PBMCs and HMVEC-L were present at the same time (p = 0.61). IL-8 accumulation in the supernatants before and after incubation with HMVEC-L is shown in Fig. 5GoB. Both PBMCs and HMVEC-L produced and secreted IL-8, and SEA increased the accumulation only when PBMCs had been incubated previously in the medium.



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  		FIGURE 5. Effect of supernatants of PBMCs incubated in the presence or absence of SEA on HMVEC-L cytotoxicity and IL-8 release. PBMCs (1.5 x 105 cells/ml) were cultured with or without SEA (10 ng/ml) for 21 h; next, supernatants were collected. A, Supernatants were incubated with radiolabeled HMVEC-L for an additional 21 h, and cytotoxicity was calculated. B, IL-8 accumulation of supernatants before (open bars) and after (hatched bars) incubation with HMVEC-L were quantitated.

 
Effect of cytokine neutralizing Abs on SEA-induced cytotoxicity and IL-8 accumulation

51Cr-labeled HMVEC-L were incubated with SEA and PBMCs in the presence of neutralizing Abs. When anti-IL-8 mAb was used, the percentage of cell lysis did not change significantly (Fig. 6GoA). However, when anti-TNF-{alpha} mAb was incubated with HMVEC-L, SEA, and PBMCs, the percentage of cell lysis was decreased in a dose-dependent manner; in addition, there were significant differences from control cultures (incubated without anti-TNF-{alpha} mAb) at concentrations >=5 µg/ml of anti-TNF-{alpha} mAb (p < 0.02) (Fig. 6GoB). The SEA-induced cytotoxicity was completely inhibited when anti-TNF-{alpha} mAb was coincubated at concentrations of >=20 µg/ml (p = 0.267). Anti-IL-ß mAb, another proinflammatory cytokine neutralizing Ab, was also tested (Fig. 6GoC). In this case, there was no significant change in cytotoxicity from control cultures grown in the absence of anti-IL-1ß mAb.



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  		FIGURE 6. Effect of cytokine neutralizing Abs on the HMVEC-L cytotoxicity induced by PBMCs and SEA. Radiolabeled HMVEC-L were incubated with PBMCs (1.5 x 105 cells/ml), SEA (10 ng/ml), and indicated concentrations of neutralizing Abs. Next, the percentage of cell lysis was calculated. A, Coincubation with anti-IL-8 mAb. B, Coincubation with anti-TNF-{alpha} mAb. C, Coincubation with anti-IL-1ß mAb.

 
IL-8 accumulation in the culture supernatants from the coincubation of HMVEC-L, SEA, and PBMCs in the presence of anti-TNF-{alpha} mAb was also quantitated (Fig. 7Go). The accumulation of IL-8 was inhibited by anti-TNF-{alpha} mAb in a dose-dependent manner and was completely inhibited at concentrations >=1 µg/ml.



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  		FIGURE 7. Effect of anti-TNF-{alpha} neutralizing Ab on IL-8 accumulation when HMVEC-L were incubated with PBMCs and SEA. HMVEC-L were incubated with 10 ng/ml of SEA, 1.5 x 105 cells/ml of PBMCs, and indicated concentrations of anti-TNF-{alpha} mAb for 21 h.

 
Effect of PMNs on HMVEC-L

HMVEC-L were incubated with various concentrations of PMNs (Fig. 8Go). In the absence of any added stimulants, the percentage of cell lysis increased with the number of PMNs added; there were significant differences from control cultures (incubated without PMNs) at concentrations >=1 x 106 cells/ml of PMNs (p < 0.002).



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  		FIGURE 8. Effect of PMNs on HMVEC-L cytotoxicity. HMVEC-L were incubated with indicated concentrations of PMNs without any stimulants for 21 h; the percentage of cell lysis was calculated as described in Materials and Methods.

 
Expression of Mac-1 and L-selectin on the surface of PMNs

Flow cytometry was performed to determine whether PMNs were activated by the purification procedure (Table IGo). The expression of Mac-1 (CD11b) was increased and the expression of L-selectin (CD62L) was decreased in CD16+ cells.


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  		Table I. Effect of density gradient centrifugation on PMNs1

 

   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
The loss of endothelial integrity by cytolysis is a common mechanism causing increased vascular permeability, and vascular damage plays an important role in the pathogenesis of vasculitis associated with ARDS (31). Infectious diseases are most commonly associated with ARDS, and Seidenfeld et al. showed that 36% of infection-induced ARDS were due to Gram-positive cocci (1).

In this study, we describe a mechanism for SEA-induced endothelial damage. TNF-{alpha}, which was produced and secreted by SEA-stimulated PBMCs, is an essential component of endothelial injury. To our knowledge, this is the first report that demonstrates a mechanism of SEA-induced endothelial damage.

Many previous reports have described PMN-dependent endothelial damage and increase in endothelial permeability (9, 16, 32). However, ARDS has been reported in patients who are neutropenic (33, 34, 35, 36), suggesting that PMNs are not essential for its development. We found that the SEA-induced cytotoxic effect occurred when the toxin was incubated with PBMCs alone and was independent of the presence of PMNs. However, the cytotoxicity was dependent upon the concentrations of both SEA and PBMCs. Furthermore, supernatants from PBMCs incubated with SEA also induced the same level of cytotoxicity in HMVEC-L. These data support the hypothesis that the ability of SEA to cause endothelial cell lysis is not related to the presence of PMNs, suggesting a possible mechanism of endothelial injury in neutropenic patients.

IL-8 has been identified as a potent PMN chemotactic and activating factor (37, 38). Our previous study showed that the concentration of IL-8 in the airspaces is elevated in patients with ARDS. Additionally, the IL-8 in the lungs of patients with ARDS associated with sepsis reached greater concentrations than in nonseptic ARDS patients (20, 21). In this study, we found that IL-8 was produced and secreted by both PBMCs and HMVEC-L without any added stimulants. Although the accumulation of IL-8 was increased in parallel with the cytotoxicity when HMVEC-L were incubated with PBMCs and SEA, neutralizing Ab for IL-8 did not reduce the cytotoxicity. These data suggest that IL-8 is not directly responsible for HMVEC-L injury.

TNF-{alpha} and IL-1ß, which are known IL-8 inducers, are produced and released by monocytic cells in response to SEA (12, 13, 14, 15). Also, both TNF-{alpha} and IL-1ß have been reported to be associated with ARDS (19). In particular, TNF-{alpha} increases pulmonary vascular permeability independent of neutrophils (39). Although the addition of anti-IL-1ß mAb did not affect HMVEC-L cytotoxicity, when anti-TNF-{alpha} mAb was coincubated with HMVEC-L, SEA, and PBMCs, the cytotoxicity decreased in a dose-dependent manner and was inhibited completely by adding 20 µg/ml of the Ab. The accumulation of IL-8 was also inhibited completely by adding 1 µg/ml of anti-TNF-{alpha} mAb. These data suggest that TNF-{alpha} is essential for the HMVEC-L cytotoxic reaction and the increase in the accumulation of IL-8. Since TNF-{alpha} also induces gene expression and the secretion of monocyte chemoattractant protein-1 by human endothelial cells (40), it is also possible that the migration of monocytes to a focus of inflammation accelerates the production and secretion of TNF-{alpha}, which could worsen the endothelial injury.

The interaction between toxic products from PMNs such as myeloperoxidase and pulmonary endothelium is thought to increase microvascular permeability to plasma proteins, and the resultant lung edema is considered to be a major component of ARDS (41, 42). Furthermore, it has been shown previously that i.v. administration of IL-8 to rabbits induced changes in the lung histology that were consistent with ARDS (43), and that IL-8 also plays a significant role in PMNs adherence to and transmigration through vascular endothelium (44). As shown in Fig. 8Go, high concentrations of purified PMNs induced HMVEC-L lysis in a dose-dependent manner. Our PMN-purification protocol, which is a standard method for in vitro study, caused an increase of Mac-1 as described previously (45), as well as a decrease of L-selectin expression on the cell surface (Table IGo). These changes in adhesion molecules were also noted on IL-8-activated PMNs (46). Therefore, it is possible that the activation of PMNs by the purification procedure participates in the PMN-induced cytotoxic effect. However, as shown in Fig. 1Go, despite any purification-induced activation, PMNs did not enhance the cytotoxic effect of PBMCs for endothelial cells. These data indicate that PBMCs play an important role in the pulmonary endothelial cytotoxicity induced by SEA.

In conclusion, we have demonstrated a mechanism of SEA-induced human lung endothelium injury. TNF-{alpha}, which is secreted by SEA-induced PBMCs, injures HMVEC-L and stimulates the production and secretion of IL-8 from PBMCs and HMVEC-L. Because PMNs can be cytotoxic to the endothelium, it is suggested that the accumulation of PMNs due to IL-8 may accelerate the cytotoxicity of HMVEC-L. From the findings we have reported here, it is expected that antagonists of TNF-{alpha} may have an important role in the treatment of SEA-induced pulmonary injury.


   Footnotes
 
1 This study was supported by National Institutes of Health Grants R29 HL55622 (to E.J.M.) and R29 HL56768 (American Heart Association, Texas Affiliate) (to A.K.). Back

2 Address correspondence and reprint requests to Dr. Edmund J. Miller, Department of Biochemistry, University of Texas Health Center, Highway 271 at Highway 155, Tyler, TX 75710. Back

3 Abbreviations used in this paper: ARDS, acute respiratory distress syndrome; PMN, polymorphonuclear cell; SEA, staphylococcal enterotoxin A; HMVEC-L, human lung microvascular endothelial cell(s); MFI, mean fluorescence intensity. Back

Received for publication December 1, 1997. Accepted for publication July 7, 1998.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Fein, A., M. Lippman, H. Holtzman. 1983. The risk factors, incidence, and prognosis of ARDS following septicaemia. Chest 40:84.
  2. Windsor, A. C. J., P. G. Mullen, A. A. Powler, H. J. Sugerman. 1993. Role of the neutrophil in adult respiratory distress syndrome. Br. J. Surg. 138:10.
  3. Murray, J. F., M. A. Matthay, J. M. Luce, M. R. Flick. 1988. An expanded definition of the adult respiratory distress syndrome. Am. Rev. Respir. Dis. 138:720.[Medline]
  4. Said, S. I., H. D. Foda. 1989. Pharmacologic modulation of lung injury. Am. Rev. Respir. Dis. 139:1553.[Medline]
  5. Pepe, P. E., R. T. Potkin, D. H. Reus, C. D. Hudson, C. J. Carrico. 1982. Clinical predictors of the adult respiratory distress syndrome. Am. J. Surg. 144:124.[Medline]
  6. Fowler, A. A., R. F. Hamman, J. T. Good, B. Benson, B. David, D. Eberke, T. C. Petty, T. M. Hyers. 1983. Adult respiratory distress syndrome: risk with common predispositions. Ann. Intern. Med. 98:593.
  7. Yokoi, K., N. Mukaida, A. Harada, Y. Watanabe, K. Matsushima. 1997. Prevention of endotoxemia-induced acute respiratory distress syndrome-like lung injury in rabbits by a monoclonal antibody to IL-8. Lab. Invest. 76:1203.
  8. Strieter, R. M., S. L. Kunkel, H. J. Showell, D. G. Remick, S. H. Phan, P. A. Ward, R. M. Marks. 1989. Endothelial cell gene expression of a neutrophil chemotactic factor by TNF{alpha}, LPS, and IL-1ß. Science 243:1467.[Abstract/Free Full Text]
  9. Schneeberger, P. M., P. van Langevelde, K. P. M. van Kessel, C. M. J. E. Vandenbroucke-Grauls, J. Verhoef. 1994. Lipopolysaccharide induces hyperadhesion of endothelial cells for neutrophils leading to damage. Shock 2:296.[Medline]
  10. Seidenfeld, J. J., D. F. Pohl, R. C. Bell, G. D. Harris, Jr W. G. Johanson. 1986. Incidence, site, and outcome of infections in patients with the adult respiratory distress syndrome. Am. Rev. Respir. Dis. 134:12.[Medline]
  11. Iandlo, J. J.. 1989. Genetic analysis of extracellular toxins of Staphylococcus aureus. Annu. Rev. Microbiol. 43:309.
  12. Björk, L., J. Andersson, M. Ceska, U. Anderson. 1992. Endotoxin and Staphylococcus aureus enterotoxin A induce different patterns of cytokines. Cytokine 4:513.[Medline]
  13. Grossman, D., R. G. Cook, J. T. Sparrow, J. A. Mollick, R. R. Rich. 1990. Dissociation of the stimulatory activities of staphylococcal enterotoxins for T cells and monocytes. J. Exp. Med. 172:1831.[Abstract/Free Full Text]
  14. Trede, N. S., A. V. Tsytsykova, T. Chatila, A. E. Goldfeld, R. S. Geha. 1995. Transcriptional activation of the human TNF-{alpha} promoter by superantigen in human monocytic cells. J. Immunol. 155:902.[Abstract]
  15. Strieter, R. M., S. W. Chensue, M. A. Basha, T. J. Standiford, J. P. Lynch, M. Baggioni, S. L. Kunkel. 1990. Human alveolar macrophage gene expression of interleukin-8 by tumor necrosis factor-{alpha}, lipopolysaccharide, and interleukin-1ß. Am. J. Respir. Cell Mol. Biol. 2:321.
  16. Gibbs, L. S., L. Lai, A. B. Malik. 1990. Tumor necrosis factor enhances the neutrophil-dependent increase in endothelial permeability. J. Cell. Physiol. 145:496.[Medline]
  17. Goldman, S. E., X. Ding, J. Campbell-Washington. 1993. TNF-{alpha} induces endothelial cell F-actin depolymerization, new actin synthesis, and barrier dysfunction. Am. J. Physiol. 264:C894.[Abstract/Free Full Text]
  18. Stephens, K. E., A. Ishizaka, J. W. Larrick, T. A. Raffin. 1988. Tumor necrosis factor causes increased pulmonary permeability and edema: comparison to septic acute lung injury. Am. Rev. Respir. Dis. 137:1364.[Medline]
  19. Suter, P. M., S. Suter, E. Girardin, P. Roux-Lombard, G. E. Grau, J. M. Dayer. 1992. High bronchoalveolar levels of tumor necrosis factor and its inhibitors, interleukin-1, interferon, and elastase, in patients with adult respiratory distress syndrome after trauma, shock, or sepsis. Am. Rev. Respir. Dis. 145:1016.[Medline]
  20. Miller, E. J., A. B. Cohen, S. Nagao, D. Griffith, R. J. Maunder, T. R. Martin, J. P. Wiener-Kronish, M. Sticherling, E. Christophers, M. A. Matthay. 1992. Elevated levels of NAP-1/interleukin-8 are present in the airspaces of patients with the adult respiratory distress syndrome and are associated with increased mortality. Am. Rev. Respir. Dis. 146:427.[Medline]
  21. Miller, E. J., A. B. Cohen, M. A. Matthay. 1996. Elevated interleukin-8 levels in pulmonary edema fluid of patients with ARDS from sepsis. Crit. Care Med. 24:1448.[Medline]
  22. Miller, E. J., A. B. Cohen, B. T. Peterson. 1996. Peptide inhibitor of interleukin-8 reduces staphylococcal enterotoxin A-induced neutrophil trafficking to the lung. Inflamm. Res. 45:393.[Medline]
  23. Boyum, A.. 1968. Isolation of mononuclear cells and granulocytes from human blood: isolation of mononuclear cells by one centrifugation and of granulocytes by combining centrifugation and sedimentation at 1 x g. Scand. J. Clin. Lab. Invest. 21:97.
  24. MacArthur, C. K., E. J. Miller, A. B. Cohen. 1987. A peptide secreted by human alveolar macrophages which releases neutrophil granule contents. J. Immunol. 139:3456.[Abstract]
  25. Hayashi, S., A. Kurdowska, E. J. Miller, M. E. Albright, B. E. Girten, A. B. Cohen. 1995. Synthetic hexa- and heptapeptides that inhibit IL-8 from binding to and activating human blood neutrophils. J. Immunol. 154:814.[Abstract]
  26. Ferrante, A., Y. H. Thong. 1978. A rapid one-step procedure for purification of mononuclear and polymorphonuclear leukocytes from human blood using modification of the Hypaque-Ficoll technique. J. Immunol. Methods 24:389.[Medline]
  27. Hayashi, S., A. Kurdowska, A. B. Cohen, M. D. Stevens, N. Fujisawa, E. J. Miller. 1997. A synthetic peptide inhibitor for {alpha}-chemokines inhibits the growth of melanoma cell lines. J. Clin. Invest. 99:2581.[Medline]
  28. Sylvester, I., J. A. Rankin, T. Yoshimura, S. Tanaka, E. J. Leonard. 1990. Selection of neutrophil attractant/activation protein by lipopolysaccharide-stimulated lung macrophages determined by both enzyme-linked immunosorbent assay and N-terminal sequence analysis. Am. Rev. Respir. Dis. 141:683.[Medline]
  29. Miller, E. J., S. Nagao, F. K. Carr, J. M. Noble, A. B. Cohen. 1996. Interleukin-8 (IL-8) is a major neutrophil chemotaxin from human alveolar macrophages stimulated with staphylococcal enterotoxin A (SEA). Inflamm. Res. 45:386.[Medline]
  30. Naitoh, K., Y. Ichigi, K. Miyake, A. Muraguchi, M. Kimoto. 1994. Signal transmission through MHC class II molecules in a human B lymphoid progenitor cell line: different signaling pathways depending on the maturational stages of B cells. Microbiol. Immunol. 38:967.[Medline]
  31. Bechard, D. E., R. P. Fairman, D. B. Hinshaw, A. A. Fowler, F. L. Glauser. 1990. In vivo interleukin-2-activated sheep lung lymph lymphocytes increase ovine vascular endothelial permeability by non-lytic mechanisms. Eur. J. Cancer. 26:1074.
  32. Bratt, J., J. Palmblad. 1997. Cytokine-induced neutrophil-mediated injury of human endothelial cells. J. Immunol. 159:912.[Abstract]
  33. Laufe, M. D., R. H. Simon, A. Flint, J. B. Keller. 1986. Adult respiratory distress syndrome in neutropenic patients. Am. J. Med. 80:1022.[Medline]
  34. Maunder, R. J., R. C. Hackman, E. Riff, R. K. Albert, S. C. Springmeyer. 1986. Occurrence of the adult respiratory distress syndrome in neutropenic patients. Am. Rev. Respir. Dis. 133:313.[Medline]
  35. Braude, S., J. Apperly, T. Krausz, J. M. Goldman, D. Royston. 1985. Adult respiratory distress syndrome after allogenic bone mallow transplantation. Lancet 1:1239.[Medline]
  36. Ognibene, F. P., S. E. Martin, M. M. Parker, T. Schlesinger, P. Roach, C. Burch, J. H. Shelhamer, J. E. Parrillo. 1986. Adult respiratory distress syndrome in patients with severe neutropenia. N. Engl. J. Med. 315:547.[Abstract]
  37. Baggioni, M., A. Waltz, S. K. Kunkel. 1989. Neutrophil-activating peptide-1/interleukin-8, a novel cytokine that activates neutrophils. J. Clin. Invest. 84:1045.
  38. Matsushima, K., J. J. Oppenheim. 1989. Interleukin-8 and MCAF: novel inflammatory cytokines inducible by IL-1 and TNF. Cytokine 1:2.[Medline]
  39. Horvath, C. J., T. J. Ferro, G. Jesmok, A. B. Malik. 1988. Recombinant tumor necrosis factor increases pulmonary vascular permeability independent of neutrophils. Proc. Natl. Acad. Sci. USA 85:9219.[Abstract/Free Full Text]
  40. Brown, Z., M. E. Gerritsen, W. W. Carley, R. M. Strieter, S. L. Kunkel, J. Westwick. 1994. Chemokine gene expression and secretion by cytokine-activated human microvascular endothelial cells: differential regulation of monocyte chemoattractant protein-1 and interleukin-8 in response to interferon-{gamma}. Am. J. Pathol. 145:913.[Abstract]
  41. Windsor, A. C. J., P. G. Mullen, A. A. Powler, H. J. Sugerman. 1993. Role of the neutrophil in adult respiratory distress syndrome. Br. J. Surg. 138:10.
  42. Murray, J. F., M. A. Matthay, J. M. Luce, M. R. Flick. 1988. An expanded definition of the adult respiratory distress syndrome. Am. Rev. Respir. Dis. 138:720.
  43. Standiford, T. J., S. L. Kunkel, R. M. Strieter. 1993. Interleukin-8: a major mediator of acute pulmonary inflammation. Reg. Immunol. 5:134.[Medline]
  44. Larsen, C. G., A. O. Anderson, E. Appella, J. J. Oppenheim, K. Matsushima. 1989. The neutrophil-activating protein (NAP-1) is also chemotactic for lymphocytes. Science 243:1045.
  45. Kujipers, T. W., A. T. J. Tool, C. E. van der Schoot, L. A. Ginsel, J. J. M. Onderwater, D. Roos, A. J. Verhoeven. 1991. Membrane surface antigen expression on neutrophils: a reappraisal of the use of surface markers for neutrophil activation. Blood 78:1105.[Abstract/Free Full Text]
  46. Detmers, P. A., D. E. Powell, A. Walz, I. Clark-Lewis, M. Baggiolini, Z. A. Cohn. 1991. Differential effects of neutrophil-activating peptide 1/IL-8 and its homologues on leukocyte adhesion and phagocytosis. J. Immunol. 147:4211.[Abstract]



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