Chemokine-Dependent Neutrophil Recruitment in a Murine Model ofLegionellaPneumonia: Potential Role of Neutrophils as Immunoregulatory Cells
| Autor: | Thomas A. Moore, Raju C. Reddy, Theodore J. Standiford, Kazuhiro Tateda, Keizo Yamaguchi, Wan C. Tsai, Jane C. Deng, Michael W. Newstead, Xianying Zeng, Gina H. Chen |
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| Rok vydání: | 2001 |
| Předmět: |
Chemokine
Neutrophils medicine.medical_treatment Neutrophile Chemokine CXCL2 Immunology Colony Count Microbial Legionella Pneumonia Microbiology Legionella pneumophila Receptors Interleukin-8B Mice medicine Animals RNA Messenger CXC chemokine receptors Receptor Lung Peroxidase biology Bacterial Infections biology.organism_classification Interleukin-12 respiratory tract diseases Infectious Diseases Cytokine Interleukin 12 biology.protein Female Parasitology Chemokines Legionnaires' Disease Chemokines CXC |
| Zdroj: | Infection and Immunity. 69:2017-2024 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.69.4.2017-2024.2001 |
| Popis: | The roles of CXC chemokine-mediated host responses were examined with an A/J mouse model ofLegionella pneumophilapneumonia. After intratracheal inoculation of 106CFU ofL. 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 againstL. pneumophilapneumonia 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 inL. pneumophilapneumonia. 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. |
| Databáze: | OpenAIRE |
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