CXC Chemokine Receptor CXCR2 Is Essential for Protective Innate Host Response in MurinePseudomonas aeruginosaPneumonia
| Autor: | Borna Mehrad, Wan C. Tsai, Michael W. Newstead, Xianying Zeng, Theodore J. Standiford, Robert M. Strieter |
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| Rok vydání: | 2000 |
| Předmět: |
Chemokine
Neutrophils Immunology Biology medicine.disease_cause CXCR3 Microbiology Receptors Interleukin-8B Mice Immune system Neutralization Tests Pneumonia Bacterial medicine Animals Humans Pseudomonas Infections RNA Messenger CXC chemokine receptors Receptor Lung DNA Primers Host Response and Inflammation Innate immune system Base Sequence Pseudomonas aeruginosa Receptors Interleukin respiratory system Mice Inbred C57BL CXCL2 Infectious Diseases biology.protein Cytokines Female Receptors Chemokine Parasitology Chemokines CXC |
| Zdroj: | Infection and Immunity. 68:4289-4296 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.68.7.4289-4296.2000 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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