title: Strain differences in alveolar neutrophil infiltration and macrophage phenotypes in an acute lung inflammation model.
abstract: Pulmonary infection is a major cause of mortality and morbidity, and the magnitude of the lung inflammatory response correlates with patient survival. Previously, we have shown that neutrophil migration into joints is regulated by arthritis severity quantitative trait loci (QTLs). However, it is unclear whether these QTLs contribute to the regulation of lung inflammation in pneumonias. Therefore, to more clearly define the factors regulating acute inflammatory responses in the lung, we examined two inbred rat strains, DA and F344, that differ in these QTLs and their susceptibility to joint inflammation. Staphylococcal cell wall components lipoteichoic acid (LTA) and peptidoglycan (PGN), administered intratracheally, significantly increased the numbers of neutrophils retrieved in the bronchoalveolar lavage fluid (BALF). F344 had approximately 10-fold more neutrophils in the BALF compared with DA (P < 0.001) and higher BALF concentrations of total protein, tumor necrosis factor-α and macrophage inflammatory protein 2. LTA/PGN administration in DA×F344 congenic strains (Cia3d, Cia4, Cia5a, and Cia6) resulted in inflammation similar to that in DA, demonstrating that the genes responsible for the differences in pulmonary inflammation are not contained within the chromosomal intervals carried by these congenic strains. Alveolar macrophages (AMs) isolated from naïve F344 stimulated in vitro with LTA/PGN produced significantly higher levels of keratinocyte-derived chemokine and macrophage inflammatory protein 2 than alveolar macrophages from DA rats. The differences were related to differential mitogen-activated protein kinase phosphorylation. We conclude that the factors contributing to inflammation can be site and challenge dependent. A better understanding of site-specific inflammation may lead to more effective treatment of acute lung inflammation and injury.
authors.affiliation: Center for Heart and Lung Research, Feinstein Institute for Medical Research, Manhasset, New York, USA. yzhang2@nshs.edu
authors.forename: Yinzhong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xinchun
authors.initials: X
authors.lastname: Lin
authors.forename: Kiyokazu
authors.initials: K
authors.lastname: Koga
authors.forename: Koichiro
authors.initials: K
authors.lastname: Takahashi
authors.forename: Helena M
authors.initials: HM
authors.lastname: Linge
authors.forename: Adriana
authors.initials: A
authors.lastname: Mello
authors.forename: Teresina
authors.initials: T
authors.lastname: Laragione
authors.forename: Percio S
authors.initials: PS
authors.lastname: Gulko
authors.forename: Edmund J
authors.initials: EJ
authors.lastname: Miller
mesh_terms: D000818:Animals; D020296:Animals, Congenic; D001169:Arthritis, Experimental; D015153:Blotting, Western / Q000379:methods*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D054426:Chemokine CXCL2 / Q000276:immunology / Q000378:metabolism; D018925:Chemokines / Q000276:immunology / Q000378:metabolism; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000378:metabolism; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000276:immunology*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010457:Peptidoglycan / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011014:Pneumonia / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D040641:Quantitative Trait Loci / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D013045:Species Specificity; D013682:Teichoic Acids / Q000494:pharmacology
chemical_list: D054426:Chemokine CXCL2; D018925:Chemokines; C513296:Cxcl2 protein, rat; D007093:Imidazoles; D008070:Lipopolysaccharides; D010457:Peptidoglycan; D011725:Pyridines; D013682:Teichoic Acids; C074302:keratinocyte-derived chemokines; C009900:lipoteichoic acid; D020928:Mitogen-Activated Protein Kinases; C093642:SB 203580