PMID- 21518788 OWN - NLM STAT- MEDLINE DCOM- 20110902 LR - 20220409 IS - 1098-5522 (Electronic) IS - 0019-9567 (Print) IS - 0019-9567 (Linking) VI - 79 IP - 7 DP - 2011 Jul TI - Monocyte chemoattractant protein 1 regulates pulmonary host defense via neutrophil recruitment during Escherichia coli infection. PG - 2567-77 LID - 10.1128/IAI.00067-11 [doi] AB - Neutrophil accumulation is a critical event to clear bacteria. Since uncontrolled neutrophil recruitment can cause severe lung damage, understanding neutrophil trafficking mechanisms is important to attenuate neutrophil-mediated damage. While monocyte chemoattractant protein 1 (MCP-1) is known to be a monocyte chemoattractant, its role in pulmonary neutrophil-mediated host defense against Gram-negative bacterial infection is not understood. We hypothesized that MCP-1/chemokine (C-C motif) ligand 2 is important for neutrophil-mediated host defense. Reduced bacterial clearance in the lungs was observed in MCP-1(-/-) mice following Escherichia coli infection. Neutrophil influx, along with cytokines/chemokines, leukotriene B(4) (LTB(4)), and vascular cell adhesion molecule 1 levels in the lungs, was reduced in MCP-1(-/-) mice after infection. E. coli-induced activation of NF-kappaB and mitogen-activated protein kinases in the lung was also reduced in MCP-1(-/-) mice. Administration of intratracheal recombinant MCP-1 (rMCP-1) to MCP-1(-/-) mice induced pulmonary neutrophil influx and cytokine/chemokine responses in the presence or absence of E. coli infection. Our in vitro migration experiment demonstrates MCP-1-mediated neutrophil chemotaxis. Notably, chemokine receptor 2 is expressed on lung and blood neutrophils, which are increased upon E. coli infection. Furthermore, our findings show that neutrophil depletion impairs E. coli clearance and that exogenous rMCP-1 after infection improves bacterial clearance in the lungs. Overall, these new findings demonstrate that E. coli-induced MCP-1 causes neutrophil recruitment directly via chemotaxis as well as indirectly via modulation of keratinocyte cell-derived chemokine, macrophage inflammatory protein 2, and LTB(4). FAU - Balamayooran, Gayathriy AU - Balamayooran G AD - Laboratory of Lung Biology, Department of Pathobiological Sciences, and Center for Experimental Infectious Disease Research, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA. FAU - Batra, Sanjay AU - Batra S FAU - Balamayooran, Theivanthiran AU - Balamayooran T FAU - Cai, Shanshan AU - Cai S FAU - Jeyaseelan, Samithamby AU - Jeyaseelan S LA - eng GR - R01 HL091958/HL/NHLBI NIH HHS/United States GR - R01 HL-091958/HL/NHLBI NIH HHS/United States GR - R01 HL-091958S1/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20110425 PL - United States TA - Infect Immun JT - Infection and immunity JID - 0246127 RN - 0 (Ccl2 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (Chemokine CXCL2) RN - 0 (NF-kappa B) RN - 0 (Vascular Cell Adhesion Molecule-1) RN - 1HGW4DR56D (Leukotriene B4) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) SB - IM EIN - Infect Immun. 2013 Nov;81(11):4323 MH - Animals MH - Bone Marrow Transplantation MH - Bronchoalveolar Lavage Fluid/immunology/microbiology MH - Chemokine CCL2/*immunology/*metabolism MH - Chemokine CXCL2/analysis MH - Escherichia coli/*immunology MH - Escherichia coli Infections/*immunology/microbiology MH - Leukotriene B4/analysis MH - Lung/immunology/metabolism/microbiology MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Mitogen-Activated Protein Kinases/metabolism MH - NF-kappa B/metabolism MH - *Neutrophil Infiltration MH - Pneumonia, Bacterial/*immunology/metabolism/microbiology MH - Vascular Cell Adhesion Molecule-1/analysis PMC - PMC3191985 EDAT- 2011/04/27 06:00 MHDA- 2011/09/03 06:00 PMCR- 2012/01/01 CRDT- 2011/04/27 06:00 PHST- 2011/04/27 06:00 [entrez] PHST- 2011/04/27 06:00 [pubmed] PHST- 2011/09/03 06:00 [medline] PHST- 2012/01/01 00:00 [pmc-release] AID - IAI.00067-11 [pii] AID - 0067-11 [pii] AID - 10.1128/IAI.00067-11 [doi] PST - ppublish SO - Infect Immun. 2011 Jul;79(7):2567-77. doi: 10.1128/IAI.00067-11. Epub 2011 Apr 25.