RGD Reference Report - Chemokine-dependent neutrophil recruitment in a murine model of Legionella pneumonia: potential role of neutrophils as immunoregulatory cells. - Rat Genome Database

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Chemokine-dependent neutrophil recruitment in a murine model of Legionella pneumonia: potential role of neutrophils as immunoregulatory cells.

Authors: Tateda, K  Moore, TA  Newstead, MW  Tsai, WC  Zeng, X  Deng, JC  Chen, G  Reddy, R  Yamaguchi, K  Standiford, TJ 
Citation: Tateda K, etal., Infect Immun. 2001 Apr;69(4):2017-24.
RGD ID: 5135252
Pubmed: PMID:11254553   (View Abstract at PubMed)
PMCID: PMC98125   (View Article at PubMed Central)
DOI: DOI:10.1128/IAI.69.4.2017-2024.2001   (Journal Full-text)

The roles of CXC chemokine-mediated host responses were examined with an A/J mouse model of Legionella pneumophila pneumonia. After intratracheal inoculation of 10(6) CFU of L. pneumophila, the bacterial numbers in the lungs increased 10-fold by day 2; this increase was accompanied by the massive accumulation of neutrophils. Reverse transcription-PCR data demonstrated the up-regulation of CXC chemokines, such as keratinocyte-derived chemokine, macrophage inflammatory protein 2 (MIP-2), and lipopolysaccharide-induced CXC chemokine (LIX). Consistent with these data, increased levels of KC, MIP-2, and LIX proteins were observed in the lungs and peaked at days 1, 2, and 2, respectively. Although the administration of anti-KC or anti-MIP-2 antibody resulted in an approximately 20% decrease in neutrophil recruitment on day 2, no increase in mortality was observed. In contrast, the blockade of CXC chemokine receptor 2 (CXCR2), a receptor for CXC chemokines, including KC and MIP-2, strikingly enhanced mortality; this effect coincided with a 67% decrease in neutrophil recruitment. Interestingly, anti-CXCR2 antibody did not affect bacterial burden by day 2, even in the presence of a lethal challenge of bacteria. Moreover, a significant decrease in interleukin-12 (IL-12) levels, in contrast to the increases in KC, MIP-2, and LIX levels, was demonstrated for CXCR2-blocked mice. These data indicated that CXCR2-mediated neutrophil accumulation may play a crucial role in host defense against L. pneumophila pneumonia in mice. The increase in lethality without a change in early bacterial clearance suggested that neutrophils may exert their protective effect not through direct killing but through more immunomodulatory actions in L. pneumophila pneumonia. We speculate that a decrease in the levels of the protective cytokine IL-12 may explain, at least in part, the high mortality in the setting of reduced neutrophil recruitment.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CXCL1HumanLegionnaires' disease  ISOCxcl1 (Mus musculus)mRNA and protein:increased expression:lungRGD 
CXCL2HumanLegionnaires' disease  ISOCxcl2 (Mus musculus)mRNA and protein:increased expression:lungRGD 
CXCL5HumanLegionnaires' disease  ISOCxcl5 (Mus musculus)mRNA and protein:increased expression:lungRGD 
CXCR2HumanLegionnaires' disease  ISOCxcr2 (Mus musculus) RGD 
Cxcl1RatLegionnaires' disease  ISOCxcl1 (Mus musculus)mRNA and protein:increased expression:lungRGD 
Cxcl1MouseLegionnaires' disease  IEP mRNA and protein:increased expression:lungRGD 
Cxcl2RatLegionnaires' disease  ISOCxcl2 (Mus musculus)mRNA and protein:increased expression:lungRGD 
Cxcl2MouseLegionnaires' disease  IEP mRNA and protein:increased expression:lungRGD 
Cxcl5MouseLegionnaires' disease  IEP mRNA and protein:increased expression:lungRGD 
Cxcl6RatLegionnaires' disease  ISOCxcl5 (Mus musculus)mRNA and protein:increased expression:lungRGD 
Cxcr2RatLegionnaires' disease  ISOCxcr2 (Mus musculus) RGD 
Cxcr2MouseLegionnaires' disease  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cxcl1  (C-X-C motif chemokine ligand 1)
Cxcl2  (C-X-C motif chemokine ligand 2)
Cxcl6  (C-X-C motif chemokine ligand 6)
Cxcr2  (C-X-C motif chemokine receptor 2)

Genes (Mus musculus)
Cxcl1  (C-X-C motif chemokine ligand 1)
Cxcl2  (C-X-C motif chemokine ligand 2)
Cxcl5  (C-X-C motif chemokine ligand 5)
Cxcr2  (C-X-C motif chemokine receptor 2)

Genes (Homo sapiens)
CXCL1  (C-X-C motif chemokine ligand 1)
CXCL2  (C-X-C motif chemokine ligand 2)
CXCL5  (C-X-C motif chemokine ligand 5)
CXCR2  (C-X-C motif chemokine receptor 2)


Additional Information