| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
*
Department of Pathology, University of Turku and Turku University Hospital, Turku, Finland; and
Chrysalis DNX Transgenics, Princeton, NJ 08540
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
|
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
The production of human group II PLA2-transgenic mice was described in detail earlier (11). Briefly, a 6.2-kb HindIII restriction fragment containing the human group II PLA2 gene was prepared and microinjected into (C57BL/6J x SJL) F2 hybrid 1 cell mouse embryos, which were then transferred to pseudopregnant ICR mice and developed to term. The transgenic founders were bred to C57BL/6J mice to produce G1 animals. Out of four transgenic lines characterized, one (line 703) was chosen for the production of the experimental animals (PLA2-transgenic and group II PLA2-deficient mice). In this line, the founder animals had significantly higher catalytic activity of PLA2 in serum than group II PLA2-deficient C57BL/6J mice (11).
The animals were housed in cages provided with Hepa-filters (ScanBur, Copenhagen, Denmark) and fed sterilized commercial chow (SDS RM1 E; Special Diet Services, Witham, U.K.). Drinking water was adjusted to pH 2.8 and autoclaved. Transgenic mice of both sexes were identified according to their specific phenotype (skin hyperplasia and almost total alopecia), and the expression of group II PLA2 was confirmed by measuring high concentrations of group II PLA2 in serum samples by time-resolved fluoroimmunoassay, as described earlier (13). Nontransgenic C57BL/6J littermates of both sexes, same age (8–10 wk), and approximately same weight were used as PLA2-deficient control animals.
Survival analysis of mice after an i.p. injection of S. aureus
S. aureus bacteria (25923; American Type Culture Collection, Manassas, VA) were cultured on brain heart infusion agar (BHIA), suspended in BHI broth (Life Technologies, Paisley, U.K.), grown to logarithmic phase, and washed three times. The OD of the final bacterial suspension was adjusted to an OD650 of 1.10 with an Ultrospec III densitometer (Pharmacia LKB, Uppsala, Sweden) and to appropriate concentrations for i.p. injections by diluting with sterile saline. After an i.p. administration of 1.0 x 108 CFU of live S. aureus/mouse, the mortality and clinical status of the transgenic and PLA2-deficient mice were registered at 6 and 12 h, and thereafter every 24 h for 7 days. Dead animals were autopsied, and samples from internal organs were taken for histological examination.
Distribution of live S. aureus in mice
Mice were given 1.0 x 107 CFU of S.
aureus as an i.p. injection, and the animals were killed 3 and
12 h later by cervical dislocation. The peritoneal cavity was
lavaged with 2 ml of sterile saline. A 0.5-ml sample was obtained from
the peritoneal lavage fluid. Small samples (
0.1 g) of the spleen and
liver were washed and homogenized in 0.4 ml ice-cold sterile saline,
and a series of 10-fold dilutions of the tissue homogenates and
peritoneal lavage fluid were plated on BHIA and cultivated for 18–24
h. The number of live bacteria in the peritoneal lavage fluid was
expressed as CFU/ml fluid and in the tissue samples as CFU/gram tissue.
In vitro bactericidal properties of serum and peritoneal lavage fluid of transgenic mice
Serum and peritoneal lavage fluid were obtained from intact mice
and infected transgenic and PLA2-deficient mice 18 h
after i.p. administration of 7.0 x 107 CFU of
S. aureus/mouse. Blood was obtained from the tip of the tail
and kept at room temperature for 30 min. Serum was separated by
centrifugation at 2,400 x g for 10 min at 6°C. The
peritoneal cavity was lavaged with 1 ml sterile saline, and the lavage
fluid was centrifuged at 14,000 x g for 10 min at
20°C to remove peritoneal cells. A total of 20 µl of serum or
peritoneal lavage fluid were mixed with 20 µl of 10 mmol/L HEPES
buffer (pH 7.4) containing 3.0 x 105 CFU of S.
aureus/ml, 10 mg/ml BSA, and 2 mmol/L CaCl2 and
incubated by shaking at 240 rpm for 2 h at 37°C (14). There were
1.5 x 105 live S. aureus/ml in the
reaction mixture at the onset of the experiment. At 20 min, 1 h,
and 2 h, samples were obtained from the reaction mixture and
diluted with ice-cold sterile saline, and the number of live bacteria
was measured as CFU/ml, as described above.
Adsorption of human group II PLA2 from sera of transgenic mice
An Ab produced against recombinant human group II PLA2 (13) was used to remove human group II PLA2 from serum of transgenic mice by immunoadsorption, as described earlier (15), with slight modifications. Briefly, 96-well plates were coated with protein A-purified rabbit anti-human group II PLA2 IgG or corresponding IgG from preimmune serum. Before use, the wells were washed three times with sterile saline. Fresh sera of transgenic mice were added into the anti-group II PLA2-IgG-coated or preimmune-IgG-coated wells, shaken for 5 min at room temperature, and transferred to another IgG-coated well. Incubation was repeated six times. The treatment with anti-human group II PLA2 IgG removed all group II PLA2 from serum and yielded group II PLA2-free transgenic mouse serum for the evaluation of bactericidal properties of serum in vitro. The concentration of human group II PLA2 in transgenic mouse sera was measured by time-resolved fluoroimmunoassay (13). To confirm the binding of human group II PLA2 from transgenic mouse serum into the anti-human group II PLA2 IgG-coated wells, Europium-labeled anti-group II PLA2 IgG was added to the wells and, after washing, time-resolved fluoresence was measured as described (13). As a rule, sequential incubation in 2–4 wells resulted in the removal of all human group II PLA2 from transgenic mouse serum.
Expression of human group II PLA2 mRNA in the liver
Transgenic and PLA2-deficient mice were killed 0, 6, 12, and 24 h after the administration of 1.0 x 107 CFU of S. aureus. Tissue samples were obtained from the liver and fixed in 4% phosphate-buffered formalin for 24–32 h for in situ hybridization or frozen in liquid nitrogen for Northern hybridization. Northern hybridization was performed as described earlier (16).
In situ hybridization was performed on formalin-fixed, paraffin-embedded tissue sections by probing with human group II PLA2 anti-sense (test) and sense (control) single-stranded RNA riboprobes. A 0.45-kb cDNA sequence covering the protein coding area of human group II PLA2 in pUC18 plasmid (17) was inserted into the HindIII and BamHI sites of pGEM-3Z transcription vector (Promega, Madison, WI). Digoxigenin (DIG)-labeled anti-sense and sense RNA probes were synthesized by in vitro transcription with T7 and SP6 RNA polymerases, respectively, by using a DIG RNA labeling kit (Boehringer Mannheim, Mannheim, Germany), and the yields were estimated by using a DIG Nucleic Acid Detection Kit (Boehringer Mannheim). The probes were purified with Quick Spin 25 columns (Boehringer Mannheim). The DIG label was detected with alkaline phosphatase-labeled anti-DIG Fab fragments by using disodium-3-(4-metoxyspiro{1,2-dioxyetane-3,2'-(5'-chloro)tricyclo[3,3,1,13,7]decan}-4-yl) phenylphosphate(CSPD; Boehringer Mannheim) as a substrate.
Concentration of human group II PLA2 and catalytic activity of PLA2 in serum after the administration of S. aureus
To study the concentration and the catalytic activity of group II PLA2 in serum in S. aureus infection, groups of transgenic and group II PLA2-deficient mice were injected i.p. with sterile saline or 1.0 x 107 CFU of S. aureus/mouse. Serum samples were collected 24 h after the administration of saline and 3, 6, 12, and 24 h after the administration of the bacteria. The concentration of immunoreactive human group II PLA2 in serum was measured as described (13). The catalytic activity of PLA2 in serum was measured as described earlier (18). Briefly, 10 µl serum samples were incubated with 100 µl substrate buffer containing mixed micelles (19) of 6 mmol 1,2-dipalmitoyl-phosphatidylcholine (Sigma, St. Louis, MO) and 1.325 µmol (250 nCi) 1-palmitoyl-2-[14C]-arachidonoylphosphatidylethanolamine (DuPont, Boston, MA) dissolved in 0.1 mol/l glycine buffer (pH 8.1) at 37°C. After 3 h of incubation, the reaction was stopped with 100 µl of Dole’s reagent, and unreacted substrate was removed by two consecutive extractions with 100 mg of dry silicic acid in 1 ml heptane. After adding 200 mg silicic acid to the reaction mixture, the samples were centrifuged at 1200 x g for 2 min at room temperature. A total of 1 ml of the heptane phase was pipetted into scintillation solution (OptiPhase, Wallac, Turku, Finland), and the radioactivity was measured by a Rackbeta liquid scintillation counter (Wallac). The activity of the enzyme is calculated as described earlier (19) and expressed as units per liter (U/L, 1 U = 1 mmol arachidonate liberated per minute). If necessary, the serum samples were diluted with saline to reach the linear range of the assay.
Response of PLA2 to cytokines
The role of cytokines in the regulation of the
PLA2-response in serum was studied by injecting 10 ng of
human recombinant IL-1 (Calbiochem, La Jolla, CA), 10 ng of IL-6
(Calbiochem), or 10 ng of TNF-
(Calbiochem) or saline
(n = 3/group) into the peritoneal cavity of transgenic
mice. The serum samples were obtained 0, 12, 24, and 48 h after
the administration of the cytokines.
Statistical analysis
Kaplan-Meier plots were constructed and Log-Rank test was used to test the differences in the survival between the transgenic and group II PLA2-deficient mice. The significances of the differences between the groups in the number of live bacteria in the peritoneal lavage fluid, spleen, liver, lung, and kidney were tested by Mann-Whitney U test. In the experiments testing the bactericidal properties of serum and peritoneal lavage fluid, the significances of the differences between the groups in the number of live bacteria were tested by one-way ANOVA. The significances of the differences between the concentrations of human group II PLA2 in serum before and after the administration of the cytokines were tested by Mann-Whitney U test. The concentrations of group II PLA2 at different time points after the injection of S. aureus are presented as a mean ± SEM. All statistical calculations were performed with Statistica Software (StatSoft, Tulsa, OK).
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
After an i.p. injection of 1.0 x 108 CFU of
S. aureus/mouse, the majority of the transgenic mice showed
minor symptoms of sepsis only, whereas 85% of the
PLA2-deficient mice developed lethargy and died within the
first 24 h after the onset of the infection. The death rate of the
transgenic mice was distinctly lower than that of the group II
PLA2-deficient mice (Fig. 1
).
At autopsy, severe congestion of the lungs, liver, and kidneys and
accumulation of hemorrhagic exudate in the pleural and peritoneal
cavities were observed in the group II PLA2-deficient
animals.
|
Three and twelve hours after the administration of 1.0 x
107 CFU of S. aureus, there were markedly lower
numbers of live bacteria in the peritoneum, spleen, liver, lung, and
kidneys in the transgenic than in the group II
PLA2-deficient mice (Table I). The number of bacteria increased in
the organs of the PLA2-deficient mice, and high numbers of
bacteria were observed especially in the peritoneal lavage fluid and
spleen of PLA2-deficient mice. On the contrary, the number
of bacteria was low in all organs of the transgenic mice examined at
3 h and decreased thereafter (data shown for 3 and 12 h).
|
Serum and peritoneal lavage fluid obtained from the transgenic
mice was highly bactericidal against S. aureus. On the
contrary, the bacteria grew well in sera of intact group II
PLA2-deficient mice. No bactericidal activity was observed
in sera or peritoneal lavage fluid of group II
PLA2-deficient mice 18 h after i.p. administration of
S. aureus (Table II). The
concentration of group II PLA2 and the bactericidal potency
of sera increased in parallel in transgenic mice after the
administration of S. aureus. Removing human group II
PLA2 by adsorption with the anti-human group II
PLA2 IgG abolished the bactericidal potency of transgenic
mouse serum (Fig. 2), whereas preimmune
rabbit IgG neither removed group II PLA2 from serum nor
affected its bactericidal properties (data not shown).
|
|
We studied the expression of group II PLA2 in the
transgenic and PLA2-deficient mice by Northern
hybridization, in situ hybridization, and by measuring the catalytic
activity of PLA2 and the concentration of immunoreactive
human group II PLA2 in serum after i.p. administration of
S. aureus. In the transgenic mice, the expression of human
group II PLA2 was induced in the liver 6–24 h after the
administration of S. aureus. Northern hybridization showed
increased signal for group II PLA2 mRNA at 12 h (Fig. 3A, lanes 2 and 3).
Markedly increased expression of human group II PLA2 was
observed in hepatocytes, with a peak at 12 h after the
administration of S. aureus, by in situ hybridization (Fig. 3, B–E). The catalytic activity of PLA2 in
serum of intact transgenic mice was 259.2 ± 25.1 U/L
(n = 46) and the catalytic activity in corresponding
sera of group II PLA2-deficient mice was 13.3 ± 0.6
U/L (n = 49). The catalytic activity of
PLA2 and the concentration of group II PLA2
increased in serum 8-fold in the transgenic animals, whereas the
group II PLA2-deficient mice did not show such a response
(Fig. 4).
|
|
Administration of biologically active doses (10 ng of
cytokine/mouse) of IL-1, IL-6, or TNF- to transgenic mice
significantly increased the concentrations of group II PLA2
in serum (Table III). At 12 h, the
levels of group II PLA2 were 7 times higher than the
pretreatment values with all cytokines studied. IL-1- and IL-6-treated
mice showed the highest serum levels of group II PLA2
24 h after the cytokine injections, whereas, in the
TNF--treated mice, group II PLA2 reached the highest
level 12 h after the administration of the cytokine. Group II
PLA2 levels decreased in all groups in 48 h but
remained above the pretreatment levels in IL-1- and IL-6-treated
animals.
|
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
The current transgenic mice provide a model to investigate biological
phenomena mediated by group II PLA2 in various diseases. An
advantage of this model is that it also provides nontransgenic mice of
the same genetic background as the transgenic animals, but lacking both
the human group II PLA2-transgene and functional endogenous
group II PLA2. Moreover, in the transgenic animals, the
concentration of group II PLA2 in serum (2500 µg/L) is
in the same range as in severe infectious diseases in humans. These
diseases include bacterial infections (the concentration of group II
PLA2 in serum 240 µg/L) (7), sepsis (880 µg/L) (9),
peritonitis (440 µg/L) (9), and typhoid fever (1440 µg/L) (21).
However, it is important to note that the catalytic activity of
PLA2 in serum of the transgenic mice is very high compared
with wild-type PLA2-expressing mice (our unpublished
observations) and that the concentration is two orders of magnitude
higher than in healthy human subjects (10 µg/L) (13). Thus, the
protective effects against bacterial infection related to the
expression of human group II PLA2 in this transgenic animal
model might lead to an overestimation of the biological efficacy of
group II PLA2, especially in relation to the other
components of innate immunity. As yet, no information is available on
the increases of PLA2 levels in normal mice following
infection or administration of cytokines.
Weinrauch et al. (14) reported that group II PLA2s of human
and rabbit are capable of killing Staphylococci and other
Gram-positive bacteria in vitro. Moreover, they reported that the
bactericidal activity against S. aureus and the
concentration of group II PLA2 in plasma increase in
experimental Escherichia coli infection of baboons (22). In
the present study, we observed that serum and peritoneal lavage fluid
obtained from transgenic mice were highly bactericidal against S.
aureus, whereas the body fluids of group II
PLA2-deficient mice did not affect the growth of bacteria.
The high bactericidal potency of serum of transgenic mice was abolished
by eliminating group II PLA2 from serum by precipitation
with anti-group II PLA2 IgG indicating that group II
PLA2 is the only substance responsible for the bactericidal
activity against S. aureus in the body fluids of the
transgenic mice. The reported LD90-values for purified
human group II PLA2 against a clinical isolate of S.
aureus were 50 µg/L (14), and concentrations of 100 µg/L
in baboon serum were required to kill S. aureus in vitro
(22). Our results support these findings. However, our results show
somewhat lower bactericidal activity for human group II
PLA2 in mouse serum, maybe due to the differences in our
respective experimental protocols and bacterial strains used. We
hypothesize that the main physiological role of increased
concentrations of group II PLA2 in serum in S.
aureus infection is the defense of the host by killing invading
bacteria.
The detailed mechanisms of bacterial killing by group II PLA2 in serum and other body fluids are not clear. On one hand, the degradation of bacterial surface phospholipids by group II PLA2 seems to be essential in bacterial killing (23). On the other hand, structural determinants of some nonmammalian group II PLA2s have bactericidal properties without any detectable enzymatic activity (24). Whereas group II PLA2 alone is able to kill Gram-positive bacteria in vitro (14, 25), the bactericidal mechanism of group II PLA2 against E. coli and other Gram-negative bacteria requires the presence of the bactericidal/permeability-increasing protein (23). Opsonization of E. coli with components of complement further potentiates the bactericidal effect (26). The dose-dependent bactericidal activity by group II PLA2 in serum and the complete removal of the bactericidal activity from serum of transgenic mice by immunoadsorption of group II PLA2 suggest a distinctive role for group II PLA2 in the killing of Gram-positive bacteria in the transgenic animals. We observed earlier that human group II PLA2 transgenic mice mounted more effective host resistance against experimental E. coli infection than group II PLA2-deficient mice (27). However, neither serum nor peritoneal lavage fluid of transgenic mice was bactericidal against E. coli in vitro.4 These findings support the bactericidal role for group II PLA2 only for Gram-positive bacteria, and suggest that there are group II PLA2-dependent mechanisms other than direct bacterial killing that may improve host resistance against Gram-negative bacterial infection.
The group II PLA2 response following the administration of S. aureus was similar to that seen after the administration of live E. coli or E. coli LPS,4 which indicates that both Gram-negative and Gram-positive bacteria are equally capable of inducing the production of group II PLA2 in transgenic mice. Elevated serum levels of group II PLA2 in transgenic mice were presumably due to the induced production of the enzyme in hepatocytes as shown by increased mRNA expression in these cells. Other cell types expressing group II PLA2 in transgenic mice, e.g., cells of the Bowman’s capsule of kidney glomeruli, bronchial epithelial cells (28), brown and white adipose tissue cells, and fibroblasts at site of infection (our unpublished observations) may act as local sources of group II PLA2 in the transgenic mice. It has been hypothesized that PLA2-deficient mice may in part compensate the defect in their group II PLA2 expression by production of other PLA2s (12). In the present study, there was no PLA2-response (increased catalytic activity of PLA2) in serum in the PLA2-deficient mice, suggesting that PLA2-deficient mice are not able to release active PLA2s into circulation in S. aureus infection.
IL-1, IL-6, and TNF- are known to mediate the expression of group II
PLA2 (5, 29). These cytokines are well-characterized
components of the nonspecific host resistance against bacterial
infections. Administration of IL-1 or IL-1ß before bacterial
inoculation improved host resistance of mice against both Gram-negative
and Gram-positive bacteria, including S. aureus (30, 31, 32, 33, 34).
TNF- improves the host defense against Chlamydia
tracomatis (35), Klebsiella pneumoniae (36), and
Streptococcus pneumoniae (37). Endogenous IL-6 protects mice
against Listeria monocytogenes infection (38). The
mechanisms of the cytokine-induced host resistance are not fully
understood. Lately, cytokine-deficient mice models have been used to
study the mechanisms involved in the innate resistance to bacterial
infection. IL-6-deficient mice are vulnerable to E. coli
(39) and L. monocytogenes (40) infections, pneumococcal
pneumonia (41) and C. trachomatis (42) infections. The
mechanism of IL-6-mediated host resistance involves improved neutrophil
response at least in L. monocytogenes (40), E.
coli (39), and C. albicans (43) infections.
TNF--deficient mice are susceptible to L. monocytogenes,
presumably due to defects in the formation of splenic germinal centers
and impaired humoral immune response (44). Interestingly,
IL-1-deficient (45), IL-6-deficient (40), and TNF--deficient (44)
mice were produced in C57BL/6J and 129/Sv background. They have a
disruption in their gene coding the endogenous group II
PLA2 (12), and, therefore, they have phenotypes of both
cytokine and PLA2 gene deficiencies. Thus, the results
obtained from the experiments done with IL-1-, IL-6-, and
TNF--deficient mice do not clarify the role of group II
PLA2 in host response, but may rather demonstrate the
effects of cytokines in host response that are independent on group II
PLA2.
The PLA2-response of transgenic mice after bacterial
challenge shown in the present study may be mediated by endogenous
cytokines, because C57BL/6J mice are able to produce endogenous IL-1,
IL-6, and TNF- in response to stimulation with endotoxin (46). We
observed a time-dependent response in serum group II PLA2
in the transgenic mice after the administration of recombinant human
IL-1, IL-6, and TNF- supporting the role of these cytokines in the
induction of group II PLA2 expression in vivo. IL-1, IL-6,
and TNF- may provide a possibility to intervene pharmacologically in
infections caused by S. aureus. However, it is important to
note that TNF may have deleterious effects in bacteremia (47) and in
the septic shock syndrome (48). The role of TNF in the group II
PLA2-dependent mechanisms of local and systemic host
defense should be considered carefully before attempts to treat
infections by this cytokine.
In conclusion, our results indicate that group II PLA2 has an important role in the host defense against S. aureus and seems to be an important member of the group of diverse proteins responsible for innate immunity (49, 50, 51).
|
Acknowledgments |
|---|
|
Footnotes |
|---|
2 Address correspondence and reprint requests to Dr. Veli J. O. Laine, Department of Pathology, University of Turku, Kiinamyllynkatu 10, 20520 Turku 52. E-mail address:
3 Abbreviations used in this paper: PLA2, phospholipase A2; BHIA, brain heart infusion agar.
4 V. J. O. Laine, D. S. Grass, and T. J. Nevalainen. Resistance of human group II phospholipase A2 transgenic mice to E. coli infection. Submitted for publication.
Received for publication December 7, 1998. Accepted for publication April 6, 1999.
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
. Infect. Immun. 55:1436.. Infect. Immun. 56:3116. in host defense against Chlamydia trachomatis. Infect. Immun. 58:1572.. Nature 381:77.[Medline]
in pathogenesis of pneumococcal pneumonia in mice. Infect. Immun. 65:257.[Abstract]
-deficient mice: a critical requirement for TNF in the formation of primary follicles, follicular dendritic cell networks and germinal centres, and in the maturation of the humoral immune response. J. Exp. Med. 184:1397. (TNF) and abrogates endotoxin-induced lethality. Shock 7:427.[Medline]
This article has been cited by other articles:
|
|
 |
|
  D. M. J. Curfs, S. A. I. Ghesquiere, M. N. Vergouwe, I. van der Made, M. J. J. Gijbels, D. R. Greaves, J. S. Verbeek, M. H. Hofker, and M. P. J. de Winther Macrophage Secretory Phospholipase A2 Group X Enhances Anti-inflammatory Responses, Promotes Lipid Accumulation, and Contributes to Aberrant Lung Pathology J. Biol. Chem., August 1, 2008; 283(31): 21640 - 21648. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. H. Salomaki, A. O. Sainio, M. Soderstrom, S. Pakkanen, J. Laine, and H. T. Jarvelainen Differential Expression of Decorin by Human Malignant and Benign Vascular Tumors J. Histochem. Cytochem., July 1, 2008; 56(7): 639 - 646. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. P. Hurley and B. A. McCormick Multiple Roles of Phospholipase A2 during Lung Infection and Inflammation Infect. Immun., June 1, 2008; 76(6): 2259 - 2272. [Full Text] [PDF]
|
|
|
|
|
|
T. Koprivnjak, C. Weidenmaier, A. Peschel, and J. P. Weiss Wall Teichoic Acid Deficiency in Staphylococcus aureus Confers Selective Resistance to Mammalian Group IIA Phospholipase A2 and Human {beta}-Defensin 3 Infect. Immun., May 1, 2008; 76(5): 2169 - 2176. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Rosengren, H. Peilot, M. Umaerus, A.-C. Jonsson-Rylander, L. Mattsson-Hulten, C. Hallberg, P. Cronet, M. Rodriguez-Lee, and E. Hurt-Camejo Secretory Phospholipase A2 Group V: Lesion Distribution, Activation by Arterial Proteoglycans, and Induction in Aorta by a Western Diet Arterioscler. Thromb. Vasc. Biol., July 1, 2006; 26(7): 1579 - 1585. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. Hunt, W. M. Nauseef, and J. P. Weiss Effect of D-Alanylation of (Lipo)Teichoic Acids of Staphylococcus aureus on Host Secretory Phospholipase A2 Action before and after Phagocytosis by Human Neutrophils. J. Immunol., April 15, 2006; 176(8): 4987 - 4994. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Piris-Gimenez, M. Paya, G. Lambeau, M. Chignard, M. Mock, L. Touqui, and P. L. Goossens In Vivo Protective Role of Human Group IIA Phospholipase A2 against Experimental Anthrax J. Immunol., November 15, 2005; 175(10): 6786 - 6791. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. K. Femling, W. M. Nauseef, and J. P. Weiss Synergy between Extracellular Group IIA Phospholipase A2 and Phagocyte NADPH Oxidase in Digestion of Phospholipids of Staphylococcus aureus Ingested by Human Neutrophils J. Immunol., October 1, 2005; 175(7): 4653 - 4661. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Levy Antimicrobial proteins and peptides: anti-infective molecules of mammalian leukocytes J. Leukoc. Biol., November 1, 2004; 76(5): 909 - 925. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Dahlin, E. M. Mager, L. Allen, Z. Tigue, L. Goodglick, M. Wadehra, and L. Dobbs Identification of Genes Differentially Expressed in Rat Alveolar Type I Cells Am. J. Respir. Cell Mol. Biol., September 1, 2004; 31(3): 309 - 316. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. P. Gimenez, Y.-Z. Wu, M. Paya, C. Delclaux, L. Touqui, and P. L. Goossens High Bactericidal Efficiency of Type IIA Phospholipase A2 against Bacillus anthracis and Inhibition of Its Secretion by the Lethal Toxin J. Immunol., July 1, 2004; 173(1): 521 - 530. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Shi, K. Takahashi, J. Dundee, S. Shahroor-Karni, S. Thiel, J. C. Jensenius, F. Gad, M. R. Hamblin, K. N. Sastry, and R. A. B. Ezekowitz Mannose-binding Lectin-deficient Mice Are Susceptible to Infection with Staphylococcus aureus J. Exp. Med., May 17, 2004; 199(10): 1379 - 1390. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Dubouix, C. Campanac, J. Fauvel, M.-F. Simon, J.-P. Salles, C. Roques, H. Chap, and N. Marty Bactericidal properties of group IIa secreted phospholipase A2 against Pseudomonas aeruginosa clinical isolates J. Med. Microbiol., December 1, 2003; 52(12): 1039 - 1045. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. J. F. Tietge, C. Maugeais, W. Cain, and D. J. Rader Acute inflammation increases selective uptake of HDL cholesteryl esters into adrenals of mice overexpressing human sPLA2 Am J Physiol Endocrinol Metab, August 1, 2003; 285(2): E403 - E411. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Murakami, S. Masuda, S. Shimbara, S. Bezzine, M. Lazdunski, G. Lambeau, M. H. Gelb, S. Matsukura, F. Kokubu, M. Adachi, et al. Cellular Arachidonate-releasing Function of Novel Classes of Secretory Phospholipase A2s (Groups III and XII) J. Biol. Chem., March 14, 2003; 278(12): 10657 - 10667. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. O. Girgis, J. J. Dajcs, and R. J. O'Callaghan Phospholipase A2 Activity in Normal and Staphylococcus aureus-Infected Rabbit Eyes Invest. Ophthalmol. Vis. Sci., January 1, 2003; 44(1): 197 - 202. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Y. Leung, X. Chen, K. M. Chu, S. T. Yuen, J. Mathy, J. Ji, A. S. Y. Chan, R. Li, S. Law, O. G. Troyanskaya, et al. Phospholipase A2 group IIA expression in gastric adenocarcinoma is associated with prolonged survival and less frequent metastasis PNAS, December 10, 2002; 99(25): 16203 - 16208. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Koprivnjak, A. Peschel, M. H. Gelb, N. S. Liang, and J. P. Weiss Role of Charge Properties of Bacterial Envelope in Bactericidal Action of Human Group IIA Phospholipase A2 against Staphylococcus aureus J. Biol. Chem., November 27, 2002; 277(49): 47636 - 47644. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. J.F. Tietge, C. Maugeais, S. Lund-Katz, D. Grass, F. C. deBeer, and D. J. Rader Human Secretory Phospholipase A2 Mediates Decreased Plasma Levels of HDL Cholesterol and ApoA-I in Response to Inflammation in Human ApoA-I Transgenic Mice Arterioscler. Thromb. Vasc. Biol., July 1, 2002; 22(7): 1213 - 1218. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Murakami, K. Yoshihara, S. Shimbara, G. Lambeau, M. H. Gelb, A. G. Singer, M. Sawada, N. Inagaki, H. Nagai, M. Ishihara, et al. Cellular Arachidonate-releasing Function and Inflammation-associated Expression of Group IIF Secretory Phospholipase A2 J. Biol. Chem., May 17, 2002; 277(21): 19145 - 19155. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Koduri, J. O. Gronroos, V. J. O. Laine, C. Le Calvez, G. Lambeau, T. J. Nevalainen, and M. H. Gelb Bactericidal Properties of Human and Murine Groups I, II, V, X, and XII Secreted Phospholipases A2 J. Biol. Chem., February 15, 2002; 277(8): 5849 - 5857. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Hurt-Camejo, G. Camejo, H. Peilot, K. Oorni, and P. Kovanen Phospholipase A2 in Vascular Disease Circ. Res., August 17, 2001; 89(4): 298 - 304. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. O. Gronroos, V. J. O. Laine, M. J. W. Janssen, M. R. Egmond, and T. J. Nevalainen Bactericidal Properties of Group IIA and Group V Phospholipases A2 J. Immunol., March 15, 2001; 166(6): 4029 - 4034. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Nyman, P. Ojala, V. J.O. Laine, and T. J. Nevalainen Distribution of Group II Phospholipase A2 Protein and mRNA in Rat Tissues J. Histochem. Cytochem., November 1, 2000; 48(11): 1469 - 1478. [Abstract] [Full Text]
|
|
|
|
 |
|
 O. Levy Antimicrobial proteins and peptides of blood: templates for novel antimicrobial agents Blood, October 15, 2000; 96(8): 2664 - 2672. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. J. O. Laine, D. S. Grass, and T. J. Nevalainen Resistance of Transgenic Mice Expressing Human Group II Phospholipase A2 to Escherichia coli Infection Infect. Immun., January 1, 2000; 68(1): 87 - 92. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Murakami, R. S. Koduri, A. Enomoto, S. Shimbara, M. Seki, K. Yoshihara, A. Singer, E. Valentin, F. Ghomashchi, G. Lambeau, et al. Distinct Arachidonate-releasing Functions of Mammalian Secreted Phospholipase A2s in Human Embryonic Kidney 293 and Rat Mastocytoma RBL-2H3 Cells through Heparan Sulfate Shuttling and External Plasma Membrane Mechanisms J. Biol. Chem., March 23, 2001; 276(13): 10083 - 10096. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
