CXC Chemokine Receptor CXCR2 Is Essential for Protective Innate Host Response in MurinePseudomonas aeruginosaPneumonia
Open Access
- 1 July 2000
- journal article
- Published by American Society for Microbiology in Infection and Immunity
- Vol. 68 (7), 4289-4296
- https://doi.org/10.1128/iai.68.7.4289-4296.2000
Abstract
Pulmonary infection due toPseudomonas aeruginosahas emerged as a leading cause of mortality. A vigorous host response is required to effectively clear the organisms from the lungs. This host defense is dependent on the recruitment and activation of neutrophils and macrophages. A family of chemotactic cytokines (chemokines) has been shown to participate in this protective response. In this study, we assessed the role of the ELR+(glutamic acid-leucine-arginine motif positive) CXC chemokines and their CXC chemokine receptor (CXCR2) in lung antibacterial host defense. The intratracheal administration ofPseudomonasto mice resulted in the time-dependent influx of neutrophils to the lung, peaking at 12 to 24 h after inoculation. The influx of neutrophils was associated with a similar time-dependent expression of the ELR+CXC chemokines, KC, macrophage inflammatory protein 2 (MIP-2), and lipopolysaccharide-induced CXC chemokine (LIX). Selective neutralization of MIP-2 or KC resulted in modest changes in neutrophil influx but no change in bacterial clearance or survival. However, neutralization of CXCR2 resulted in a striking increase in mortality, which was associated with a marked decrease in neutrophil recruitment and bacterial clearance. Conversely, the site-specific transgenic expression of KC resulted in enhanced clearance of bacteria afterPseudomonaschallenge. This study indicates that ELR+CXC chemokines are critical mediators of neutrophil-mediated host defense inPseudomonaspneumonia.Keywords
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