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• W2157511209 abstract "Abstract In prior studies, we demonstrated that 1) CXCL1/KC is essential for NF-κB and MAPK activation and expression of CXCL2/MIP-2 and CXCL5/LPS-induced CXC chemokine in Klebsiella-infected lungs, and 2) CXCL1 derived from hematopoietic and resident cells contributes to host immunity against Klebsiella. However, the role of CXCL1 in mediating neutrophil leukotriene B4 (LTB4), reactive oxygen species (ROS), and reactive nitrogen species (RNS) production is unclear, as is the contribution of these factors to host immunity. In this study, we investigated 1) the role of CXCL1 in LTB4, NADPH oxidase, and inducible NO synthase (iNOS) expression in lungs and neutrophils, and 2) whether LTB4 postinfection reverses innate immune defects in CXCL1−/− mice via regulation of NADPH oxidase and iNOS. Our results demonstrate reduced neutrophil influx, attenuated LTB4 levels, and decreased ROS and iNOS production in the lungs of CXCL1−/− mice after Klebsiella pneumoniae infection. Using neutrophil depletion and repletion, we found that neutrophils are the predominant source of pulmonary LTB4 after infection. To treat immune defects in CXCL1−/− mice, we intrapulmonarily administered LTB4. Postinfection, LTB4 treatment reversed immune defects in CXCL1−/− mice and improved survival, neutrophil recruitment, cytokine/chemokine expression, NF-κB/MAPK activation, and ROS/RNS production. LTB4 also enhanced myeloperoxidase, H2O2, RNS production, and bacterial killing in K. pneumoniae-infected CXCL1−/− neutrophils. These novel results uncover important roles for CXCL1 in generating ROS and RNS in neutrophils and in regulating host immunity against K. pneumoniae infection. Our findings suggest that LTB4 could be used to correct defects in neutrophil recruitment and function in individuals lacking or expressing malfunctional CXCL1." @default.
• W2157511209 created "2016-06-24" @default.
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• W2157511209 date "2012-04-01" @default.
• W2157511209 modified "2023-10-16" @default.
• W2157511209 title "Intrapulmonary Administration of Leukotriene B4 Augments Neutrophil Accumulation and Responses in the Lung to <i>Klebsiella</i> Infection in CXCL1 Knockout Mice" @default.
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• W2157511209 doi "https://doi.org/10.4049/jimmunol.1101985" @default.
• W2157511209 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3311767" @default.
• W2157511209 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22379035" @default.
• W2157511209 hasPublicationYear "2012" @default.
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