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TVW Telethon Institute for Child Health Research, and Centre for Child Health Research, University of Western Australia, Perth, Western Australia, Australia; and
Glaxo Wellcome Research and Development SA, Geneva, Switzerland
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Abstract |
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 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
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Introduction |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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The present experiments focus on DC in the mucosa of the conducting airways, which is under continuous exposure to a wide range of pathogenic and nonpathogenic Ags present in ambient air. The lining airway epithelium of adult experimental animals and humans contains a network of DC which comprise in the range of 400–800 DC/mm2 epithelial surface, comparable to the Langerhans cell network of the epidermis (10, 11). The airway epithelial DC turn over more rapidly than DC at any other peripheral tissue site with the possible exception of the intestinal wall (12), and accumulating evidence suggests that this continuous and rapid population renewal is a direct result of the intensity of local antigenic stimulation (13). Moreover, we have previously reported that local challenge of the airway mucosa with bacterial, viral, or soluble protein Ags results in the immediate recruitment of large numbers of fresh DC with kinetics equivalent to neutrophils (14, 15), underscoring the potential importance of these cells in local immune defense.
Here we present data on the ex vivo responsiveness of freshly isolated tracheal epithelial DC to CC vs CXC chemokines and demonstrate the utility of the selective CCR1 and CCR5 antagonist Met-RANTES in blocking the recruitment of DC precursors into resting airway epithelium and during acute inflammation induced by a bacterial stimulus. However, recruitment of DC in response to challenge with live virus or a soluble recall Ag was not affected by Met-RANTES, suggesting that the mechanism(s) used for attraction of DC into airway tissues during inflammation are stimulus dependent.
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Materials and Methods |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Inbred PVG rats were bred free of common rat pathogens in house at the TVW Telethon Institute for Child Health Research (Perth, Australia), and housed as conventional animals under barrier-controlled conditions. Animals 8–16 wk old were used. All animal experimentation was approved by the Institutional Animal Ethics and Experimentation Committee, operating under guidelines set by the National Health and Medical Research Council of Australia.
Monoclonal Abs and cell-staining reagents
Methods used for immunostaining, quantification of endocytic activity via uptake of FITC-dextran, and the details of mouse mAbs to rat cell surface markers, were described previously (16). Cell samples were analyzed for surface fluorescence by flow cytometry using a FACSCalibur (BD Biosciences, Mountain View, CA).
Cell preparations
Cell isolation procedures were conducted in 0.2% BSA (PBS/BSA)
or a solution of 11 mM D-glucose, 5.5 mM KC1, 137 mM NaC1,
25 mM Na2HPO4, and 5.5 mM
NaH2PO4·2H2O
(GKN) supplemented with 5% FCS (GKN/FCS) or 0.2% BSA (GKN/BSA) as
indicated. Collagenase digests of sliced trachea were prepared by a
modification of the method described in (17). Digests were
depleted of endogenous macrophages by plastic adherence for 45 min in
GKN/FCS and washed in GKN/BSA, and residual contaminating B cells were
removed by labeling with the OX12 mAb (anti-rat 
light chain)
followed by magnetic depletion using anti-mouse IgG-coated MACS
beads (Miltenyi Biotec, Bergisch Gladbach, Germany). After this
procedure, contaminating macrophages were undetectable and B cells were
<5%. The depleted cells were then washed and incubated with GAM-PE to
label residual OX12+ B cells, followed by
blocking with 10% normal mouse serum and incubation with OX6-FITC to
label MHC class II+ cells.
OX6+OX12- DC were then
purified by dual-parameter cell sorting (Epics Elite; Coulter, Orlando,
FL) as detailed previously (16) using chilled GKN plus
20% FCS as the collection medium.
Immunohistochemical analysis
Tracheas were removed and immediately fixed in cold ethanol for 30 min. The tissue was then rehydrated in PBS, embedded in 100% OCT, and frozen in liquid nitrogen-cooled isopentane. Tangential sections 8–10 µm thick were cut on a cryostat and immunostained, and quantification of DC conducted as detailed previously (11).
Preparation, fixation, and immunostaining of lung sections and epidermal sheets, and subsequent enumeration of DC and Langerhans cells, was as detailed previously (10, 11).
Met-RANTES treatment
Met-RANTES was produced as described before (18). Rats were inoculated i.p. with 0.5 ml PBS or an equivalent volume containing varying levels of Met-RANTES, as specified in the figure legends.
In vivo challenge systems
Bacterial model.
This was based on the system detailed in Ref. 14 .
Moraxella catarrhalis was grown in Mueller-Hinton broth and
suspended at 
109 CFU/ml. The suspension was
heated at 60°C for 1 h and passed through a 26-gauge
needle several times to break up bacterial clumps. Rats were exposed by
aerosol to the suspension for 1 h using a Tri-R inhalation
exposure apparatus (Tri-R Instruments, New York, NY).
Viral model. This was based on the system used in Ref. 15 . Sendai virus was grown for 3 days in the allantoic cavity of eggs and stored in allantoic fluid at -70°C until used. Adult rats were inoculated intranasally with 103 hemagglutination U in 50 µl virus containing allantoic fluid. Control animals were similarly inoculated with virus-free allantoic fluid. Infection of airway epithelium was confirmed by staining with mAb WS16 against the nucleoprotein Ag of Sendai virus (provided by Dr. A. Portner, St. Jude Children’s Research Hospital, Memphis, TN). There was no influx of DC or T cells into the airway epithelium of control animals.
Soluble protein recall Ag. Animals were primed i.p. with 100 µg OVA (Sigma, St. Louis, MO) in 0.5 ml PBS containing 10 mg aluminum hydroxide (Amphojel; Wyeth-Ayerst Laboratories, Marietta, PA). After 14 days, the animals were challenged for 30 min with an aerosol of 1% (w/v) OVA in PBS.
DC chemotaxis
The assay system was as detailed in Ref. 15 .
Briefly, DC were enriched to 
92% purity from collagenase digests of
respiratory tract tissue by flow cytometry as detailed in Ref.
16 . Medium (RPMI plus 2.5% FCS), 600 µ l, containing
putative chemoattractant was placed in the lower chamber of a Costar
Transwell, and 105 enriched DC in 100 µl medium
were placed in the insert; after incubation for 1 h at 37°C, the
top surface of the inserts was washed free of cells an the insert was
fixed in cold ethanol for 10 min. The polycarbonate membranes were
excised, and the contralateral surface immunostained with mAb Ox6;
migrating cells were observed under a x25 objective and enumerated as
mean number cells/high power field.
The chemoattractants used were: 10% zymosan-activated normal rat serum
(the active agents being complement cleavage products, in
particular C5a); fMLP (10-8 M; Sigma); rat
monocyte chemotactic protein (MCP)-1 (CCL2), growth-related oncogene
(GRO)/cytokine-induced neutrophil chemoattractant (CINC) (CXCL1),
GRO-
(CXCL2) (all at 100 ng/ml), rat RANTES (CCL5) (200 ng/ml), and
murine eotaxin (CCL11) (100 ng/ml; Peprotech (London, U.K.); human
MCP-4 (CCL13) (100 ng/ml; Glaxo Wellcome, Geneva, Switzerland); and
murine macrophage-inhibitory protein (MIP)-3
(100 ng/ml; Serono,
Geneva, Switzerland).
RT-PCR
Total RNA was prepared from samples of
105 DC (purity, 92–94%) by RNAzol B
extraction (Biogenesis, Poole, U.K.) according to the manufacturer’s
instructions, and mRNA was reverse transcribed to cDNA. Amplification
of mRNA specific for chemokines was performed by PCR using cDNA
serially diluted in reaction buffer to ensure that PCR
products were being analyzed under nonsaturating conditions.
Amplification of -actin mRNA was also conducted as an internal
control for efficiency of RNA extraction and reverse transcription. The
sequence of PCR primer pairs used are listed in Table I
below. PCR products were separated and
visualized on an ethidium bromide-stained agarose gel. PCR included RT
control (no RNA) and a PCR-negative control (not shown), and as a
positive control cDNA from alveolar macrophages hyperstimulated with
LPS/IFN-
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Results |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Ox6+ airway DC were sorted to 96%
homogeneity using gating parameters shown in Fig. 1A; Ox6 expression within the
population is shown as a histogram in Fig. 1D. Endocytic
activity was assessed as per Ref. 16 comparing uptake of
FITC-dextran at 4°C (Fig. 1B; background binding control)
vs 37°C (Fig. 1C) for 10 min in the presence of trypan
blue to quench cell surface fluorescence. On the order of 50% of the
DC exhibited high levels of endocytosis. Fig. 1, E and
F, illustrates expression of CD86 and CD80, respectively.
The hallmark features of this DC population are thus moderate to high
expression levels of MHC class II and a similar distribution of
endocytic activity, coupled with low levels of expression of
costimulator molecules CD80 and CD86. These features are consistent
with the presence within this population of a high proportion of
"immature" DC.
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are derived from groups of five
animals and are shown as mean ± SEM; respective results were
verified by replication 3 times except for experiments in Fig. 6
which was performed twice with comparable findings.
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In the experiments in Fig. 2, adult
control rats were dosed with Met-RANTES as shown for 1, 2, 4, or 8 days
before sacrifice, and airway intraepithelial DC density was assessed in
immunostained frozen tracheal sections. Continuous treatment with the
chemokine receptor antagonist for 4 days resulted in a 48% reduction
in airway epithelial DC density, and a further 4 days of treatment
extended the reduction to 60–65%. In one series of experiments, the
surface phenotypes of the airway DC that persist in the face of
Met-RANTES treatment were compared with the starting population. The
surface markers assessed were MHC class II (mAb Ox6), CD86 (mAb 24F),
ICAM-1 (mAb IA-29), and CD11b/c (Ox42), as detailed in Ref.
16 . No consistent differences were detected (data not
shown).
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contrasts the effects of
Met-RANTES on DC population density in resting airway (tracheal)
epithelium vs peripheral lung and epidermis of the same animals. Eight
days of continuous treatment with the chemokine receptor antagonist
reduced baseline population levels in the airway and peripheral lung by
on the order of 60 and 30%, respectively, but had no detectable
effects on the Langerhans cell network in the epidermis.
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Exposure of adult rats to an aerosol of heat-killed
Moraxella catarrhalis triggers rapid recruitment of a wave
of DC into the airway epithelium (Fig. 4)
as reported earlier (1). Preinjection of animals with 10
µg Met-RANTES 30 min before aerosol exposure results in
dose-dependent attenuation of the DC response, as measured 24 h
later. In addition, follow-up experiments (not shown) were performed
involving assessment of DC numbers at the 3- and 6-h time points post
M. catarrhalis exposure in the presence and/or absence of
Met-RANTES. These indicated that the small amount of DC recruitment
that occurred in the treated animals peaked within the initial 3-h
period and that DC numbers remained stable over the ensuing
21 h.
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85% of the DC influx, and this was
used for subsequent experiments. As shown in Fig. 5, administration of 50 µg Met-RANTES
24 h before M. catarrhalis challenge was essentially as
effective as administration immediately before exposure, and inhibition
was still observed 3 days after a single treatment with the chemokine
receptor antagonist.
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As shown in Table II
, both of these challenge protocols result in
significant DC recruitment into the tracheal epithelium. However,
unlike the situation noted above with M. catarrhalis, DC
recruitment in response to Sendai virus or OVA challenge was not
sensitive to Met-RANTES treatment.
In vitro chemokine production and responsiveness of freshly prepared resting airway DC and airway DC 24 h after M. catarrhalis exposure
The experiments in Fig. 6 contrast
the responsiveness of rat tracheal DC to a range of stimuli comprising
complement cleavage products (generated via zymosan activation of
normal rat serum), FMLP, and a selected range of CC and CXC chemokines.
Responsiveness was consistently observed to all agents tested except
the CXC chemokines.
In parallel, production of cytokine-specific mRNA was assessed in
highly purified tracheal DC by RT-PCR using the range of rat primer
sequences available to us. Those tested were MIP-1, MIP-1, MIP-2,
MCP-1, and GRO/CINC. Message production for all the latter was
detected in resting DC (Fig. 7), and
comparable expression of the same message species was observed in DC
collected post-M. catarrhalis exposure.
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Discussion |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Thus, immature precursor DC are attracted into inflammatory sites via a set of chemokines for which they express receptors exclusively at this early stage of differentiation, but which are down-regulated as they mature and are replaced by others which respond to chemokine signals favoring migration to DLN, such as secondary lymphoid tissue-derived chemokine produced by lymphatic endothelial cells (19) and EBI-1 ligand chemokine produced in the T cell areas of draining nodes (3, 6, 20). However, there is very limited information available on the applicability of this model to specific tissue microenvironments in vivo or on how precursor DC are attracted into resting tissues to maintain basal levels of DC during the steady state.
This study addresses some of the relevant issues in relation to the DC
within the epithelium lining the conducting airways. This DC population
is of major importance to host survival because it defends the most
delicate epithelial interface with the external environmental, which is
constantly challenged by incoming Ags. Under steady state conditions.
85% of the airway DC population turns over at a uniquely rapid
rate, being renewed every 36–48 h by influxing precursors from the
bone marrow (12). The minority (long-lived) resident
population has not been studied in detail.
A series of experiments in this study examined aspects of the in vivo
regulation of this normal process, using Met-RANTES, a potent CCR
antagonist (18). In the human system, Met-RANTES retains
high affinity binding to CCR1 and CCR5 and has weak affinity for CCR3
(21, 22). High affinity is retained for murine CCR1 and
CCR5, as shown in earlier in vivo studies that demonstrated inhibition
of chemotaxis of murine splenocytes by RANTES and MIP-1 with
nanomolar quantities of Met-RANTES, whereas Met-RANTES is ineffective
on murine CCR3 (A. Proudfoot, manuscript in preparation). Met-RANTES is
also highly effective in inhibition of chemotaxis of leukocytes in vivo
in the rat (23). The principal effects of Met-RANTES in
the rat are therefore most likely mediated through CCR1 and CCR5. As
shown in Fig. 2, chronic administration of Met-RANTES reduces the
baseline DC population at this site to 40% of starting numbers,
providing for the first time evidence that interactions between CCR1
and CCR5 and their appropriate ligands play a major role in steady
state regulation of mucosal DC populations.
Further evidence in support of this suggestion was provided in the
experiments of Fig. 6. Previous functional studies on DC populations
from the respiratory tract have been restricted to mixed populations
from airways and parenchymal tissues derived by enzymatic dispersion of
whole lung which by a variety of criteria express the "immature" DC
phenotype (16). However, in the experiments in Fig. 6, we
have for the first time prepared purified airway (tracheal) DC
separately in sufficient numbers for study. These cells were responsive
to the CC chemokines MCP-1 (CCR2), MCP-4 (CCR2 and 3), eotaxin (CCR3),
and RANTES (CCR1, 3, and 5; see Ref. 24), suggesting a
pattern of chemokine receptor expression on airway DC comparable to
that of in vitro-derived DC (3, 4, 5, 6), and also to the mixed
DC population isolated from whole lung digests (16). The
respiratory tract DC populations were also unresponsive to a range of
CXC chemokines.
These findings are collectively consistent with those from studies that
indicate CCR1 and CCR5 expression on in vitro-derived immature DC
(2, 4, 5, 6). They additionally suggest that constitutive
production of one or more of the respective ligands for these receptors
occurs continuously within the resting airway epithelium. The nature of
the cell types responsible for production of these chemokines in the
steady state remains to be defined, but the presence of a range of
chemokine-specific mRNA species in DC freshly isolated from trachea
(Fig. 7) suggests that these cells constitute one of the potential
sources (see also Ref. 5), and if so the airway epithelial
DC network may to an extent be self-regulatory in the steady state.
As shown in Fig. 2, on the order of 40% of the resident DC in the
resting airway epithelium are Met-RANTES insensitive. One plausible
explanation for this finding is that the 40% of the population that is
Met-RANTES resistant is maintained by chemokines other than those
dependent on CCR1/5, e.g., CCR2, which is expressed on monocyte-derived
immature DC (5, 6). This receptor binds MCP-1 which is
reported to be produced constitutively by airway epithelial cells
(25).
Also, the DC population in the peripheral lung and epidermis were less
sensitive to Met-RANTES than their counterparts in the airway
epithelium (Fig. 3). In this context, we have previously reported
comparative half-life values of 1.5–2, 3–4, and >15 days,
respectively, for airway, peripheral lung, and epidermal DC in the same
rats (12), and the relative levels of sensitivity to
Met-RANTES treatment during an 8-day period in trachea vs peripheral
lung may be a direct reflection of these differences in turnover rates.
Other more detailed studies on epidermal Langerhans cell turnover rates
have yielded half-life figures in the range of 21–30 days
(26), and the changes expected during an 8-day period in
such a stable population may not be detectable with the methods used,
even if the Met-RANTES were highly effective in blocking precursor
recruitment.
The experiments in Figs. 4 and 5 examined airway DC recruitment during
acute inflammation induced by inhalation of a bacterial stimulus. We
have previously reported that the influx of DC in this system occurs
with kinetics initially equivalent to polymorphonuclear neutrophils
(PMN); the influx occurs as a wave of cells that peaks at 2 h
post-cessation of exposure and remains stable up to 48 h, before
declining to baseline levels as the recruited cells migrate on to DLN
(14). As shown in Fig. 4, this response is almost
completely inhibitable by Met-RANTES, indicating the prime importance
of CCR1/5 receptors and their ligands in this particular inflammatory
response. The effects of the chemokine receptor antagonist are
surprisingly long lasting, with 50% of the maximal inhibition retained
when Met-RANTES was administered 3 days before Ag challenge. Although
no pharmacokinetic data are available to date for modified chemokines
such as Met-RANTES, it is possible that through their interactions with
cell surface glycosaminoglycans they become immobilized on tissue
surfaces (27), allowing their slow release into the
circulation.
We have additionally reported that intranasal challenge with live Sendai virus (15, 28), or aerosol challenge of primed animals with the soluble Ag OVA (15) also recruits large numbers of DC into the airway epithelium. In the case of the bacterial stimulus, the DC were accompanied by PMN (14, 15) whereas in the viral model the accompanying cells were PMN, NK, and T cells (15, 28), vs T cells and eosinophils in the OVA model (15). In relation to the experiments with M. catarrhalis, we have additionally demonstrated that Met-RANTES blocked up to 65% of the PMN response (data not shown). It is theoretically possible that PMN may be the source of the chemokines for DC recruitment and hence it is conceivable that the effects of Met-RANTES in this system are secondary to its effects on PMN recruitment. Arguing against this possibility are our previous findings indicating that initiation of DC recruitment in this model is coincident with, or even precedes, PMN recruitment (14). It is possible that T cells and eosinophils may play a role in DC recruitment process in the other models, but more detailed experiments would be required to test this proposition.
As shown in Table II, pretreatment with Met-RANTES using the protocol
that virtually abrogates airway DC recruitment induced by a bacterial
stimulus had no effect in the Sendai or OVA models. This indicates that
CCR1/5 receptors and their ligands are not required for DC recruitment
in these latter systems, suggesting therefore that alternative
receptors and/or chemokines are involved, which is reflected in part by
the differing cell combinations recruited by each stimulus. One set of
likely possibilities with respect to DC attraction by Sendai and OVA
would appear to be CCR2, CCR3, and possibly CCR6 receptors, which are
expressed on in vitro-derived immature DC (2). The
chemokine-binding properties of CCR5 overlap significantly with those
of CCR1, whereas MCP-1 activates only CCR2 and eotaxin activates CCR3,
and these two chemokines (as shown in Fig. 6 and Ref. 15)
chemoattract immature lung/airway DC in rat. Note also the
positive effects of MIP-3 (which activates CCR6) in Fig. 6.
In conclusion, these studies demonstrate that attraction of DC precursors into rat airway epithelium is governed by a highly flexible chemokine receptor/ligand program. Thus, steady state DC recruitment uses CCR1/5 receptors for maintenance of up to 60% of the baseline population and presumably relies on constitutive chemokine production within the epithelium by one or more cell types which may include the resident DC themselves. During acute bacterial inflammation, reliance on CCR1/5 and their ligands for DC recruitment increases to approach 100%, but during primary viral infection or challenge with soluble recall, Ag alternative chemokine receptors/ligands are used; it is also possible that a distinct subset of DC that are not present in resting or bacterial-stimulated epithelium may be recruited in these latter situations. The ultimate result of this flexibility is that regardless of the stimulus or the nature of the final effector cell combinations that appear at the challenge site, DC appear always to comprise a significant component of the cellular influx and as such represent the ultimate "default" component of the host cellular inflammatory response. This property of DC is consistent with the suggestion that one of their prime roles is provision of the linkage between the adaptive and innate arms of the host immunoinflammatory response (29, 30).
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Footnotes |
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2 Current address: Department of Medicine, University of Western Australia, Perth, Western Australia, Australia.
3 Current address: Department Microbiology, University of Western Australia, Perth, Western Australia, Australia.
4 Current address: Serono Pharmaceutical Research Institute, Geneva, Switzerland.
5 Address correspondence and reprint requests to Dr. Patrick G. Holt, Division of Cell Biology, TVW Telethon Institute for Child Health Research, P.O. Box 855, West Perth, Western Australia 6872, Australia. E-mail address: patrick{at}ichr.uwa.edu.au
6 Abbreviations used in this paper: DC, dendritic cells; DLN, draining lymph nodes; MIP, macrophage-inflammatory protein; MCP, monocyte chemotactic protein; GRO, growth-related oncogene; PMN, polymorphonuclear neutrophil; CINC, cytokine-induced neutrophil chemoattractant.
Received for publication November 29, 2000. Accepted for publication April 27, 2001.
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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E. L. Turnbull, U. Yrlid, C. D. Jenkins, and G. G. MacPherson Intestinal Dendritic Cell Subsets: Differential Effects of Systemic TLR4 Stimulation on Migratory Fate and Activation In Vivo J. Immunol., February 1, 2005; 174(3): 1374 - 1384. [Abstract] [Full Text] [PDF]
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P. Puneet, S. Moochhala, and M. Bhatia Chemokines in acute respiratory distress syndrome Am J Physiol Lung Cell Mol Physiol, January 1, 2005; 288(1): L3 - L15. [Abstract] [Full Text] [PDF]
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 B.-C. Chiu, C. M. Freeman, V. R. Stolberg, J. S. Hu, K. Zeibecoglou, B. Lu, C. Gerard, I. F. Charo, S. A. Lira, and S. W. Chensue Impaired Lung Dendritic Cell Activation in CCR2 Knockout Mice Am. J. Pathol., October 1, 2004; 165(4): 1199 - 1209. [Abstract] [Full Text] [PDF]
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C. A. Bonville, V. K. Lau, J. M. DeLeon, J.-L. Gao, A. J. Easton, H. F. Rosenberg, and J. B. Domachowske Functional Antagonism of Chemokine Receptor CCR1 Reduces Mortality in Acute Pneumovirus Infection In Vivo J. Virol., August 1, 2004; 78(15): 7984 - 7989. [Abstract] [Full Text] [PDF]
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H. Ichiyasu, J. M. McCormack, K. M. McCarthy, D. Dombkowski, F. I. Preffer, and E. E. Schneeberger Matrix Metalloproteinase-9-Deficient Dendritic Cells Have Impaired Migration through Tracheal Epithelial Tight Junctions Am. J. Respir. Cell Mol. Biol., June 1, 2004; 30(6): 761 - 770. [Abstract] [Full Text] [PDF]
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 A. Rial, D. Lens, L. Betancor, H. Benkiel, J. S. Silva, and J. A. Chabalgoity Intranasal Immunization with a Colloid-Formulated Bacterial Extract Induces an Acute Inflammatory Response in the Lungs and Elicits Specific Immune Responses Infect. Immun., May 1, 2004; 72(5): 2679 - 2688. [Abstract] [Full Text] [PDF]
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S. J. Turner, N. L. La Gruta, J. Stambas, G. Diaz, and P. C. Doherty Differential tumor necrosis factor receptor 2-mediated editing of virus-specific CD8+ effector T cells PNAS, March 9, 2004; 101(10): 3545 - 3550. [Abstract] [Full Text] [PDF]
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 S. C. Robinson, K. A. Scott, J. L. Wilson, R. G. Thompson, A. E. I. Proudfoot, and F. R. Balkwill A Chemokine Receptor Antagonist Inhibits Experimental Breast Tumor Growth Cancer Res., December 1, 2003; 63(23): 8360 - 8365. [Abstract] [Full Text] [PDF]
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R. B. Mailliard, Y.-I. Son, R. Redlinger, P. T. Coates, A. Giermasz, P. A. Morel, W. J. Storkus, and P. Kalinski Dendritic Cells Mediate NK Cell Help for Th1 and CTL Responses: Two-Signal Requirement for the Induction of NK Cell Helper Function J. Immunol., September 1, 2003; 171(5): 2366 - 2373. [Abstract] [Full Text] [PDF]
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K. Y. Vermaelen, D. Cataldo, K. Tournoy, T. Maes, A. Dhulst, R. Louis, J.-M. Foidart, A. Noel, and R. Pauwels Matrix Metalloproteinase-9-Mediated Dendritic Cell Recruitment into the Airways Is a Critical Step in a Mouse Model of Asthma J. Immunol., July 15, 2003; 171(2): 1016 - 1022. [Abstract] [Full Text] [PDF]
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 J. C. Huh, D. H. Strickland, F. L. Jahnsen, D. J. Turner, J. A. Thomas, S. Napoli, I. Tobagus, P. A. Stumbles, P. D. Sly, and P. G. Holt Bidirectional Interactions between Antigen-bearing Respiratory Tract Dendritic Cells (DCs) and T Cells Precede the Late Phase Reaction in Experimental Asthma: DC Activation Occurs in the Airway Mucosa but Not in the Lung Parenchyma J. Exp. Med., July 7, 2003; 198(1): 19 - 30. [Abstract] [Full Text] [PDF]
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R. Pabst, A. Luhrmann, I. Steinmetz, and T. Tschernig A Single Intratracheal Dose of the Growth Factor Fms-Like Tyrosine Kinase Receptor-3 Ligand Induces a Rapid Differential Increase of Dendritic Cells and Lymphocyte Subsets in Lung Tissue and Bronchoalveolar Lavage, Resulting in an Increased Local Antibody Production J. Immunol., July 1, 2003; 171(1): 325 - 330. [Abstract] [Full Text] [PDF]
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J. Reibman, Y. Hsu, L. C. Chen, B. Bleck, and T. Gordon Airway Epithelial Cells Release MIP-3{alpha}/CCL20 in Response to Cytokines and Ambient Particulate Matter Am. J. Respir. Cell Mol. Biol., June 1, 2003; 28(6): 648 - 654. [Abstract] [Full Text] [PDF]
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G. de la Rosa, N. Longo, J. L. Rodriguez-Fernandez, A. Puig-Kroger, A. Pineda, A. L. Corbi, and P. Sanchez-Mateos Migration of human blood dendritic cells across endothelial cell monolayers: adhesion molecules and chemokines involved in subset-specific transmigration J. Leukoc. Biol., May 1, 2003; 73(5): 639 - 649. [Abstract] [Full Text] [PDF]
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N. Omata, M. Yasutomi, A. Yamada, H. Iwasaki, M. Mayumi, and Y. Ohshima Monocyte Chemoattractant Protein-1 Selectively Inhibits the Acquisition of CD40 Ligand-Dependent IL-12-Producing Capacity of Monocyte-Derived Dendritic Cells and Modulates Th1 Immune Response J. Immunol., November 1, 2002; 169(9): 4861 - 4866. [Abstract] [Full Text] [PDF]
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