title: A macrophage subpopulation recruited by CC chemokine ligand-2 clears apoptotic cells in noninfectious lung injury.
abstract: CC chemokine ligand-2 (CCL2)/monocyte chemoattractant protein (MCP)-1 expression is upregulated during pulmonary inflammation, and the CCL2-CCR2 axis plays a critical role in leukocyte recruitment and promotion of host defense against infection. The role of CCL2 in mediating macrophage subpopulations in the pathobiology of noninfectious lung injury is unknown. The goal of this study was to examine the role of CCL2 in noninfectious acute lung injury. Our results show that lung-specific overexpression of CCL2 protected mice from bleomycin-induced lung injury, characterized by significantly reduced mortality, reduced neutrophil accumulation, and decreased accumulation of the inflammatory mediators IL-6, CXCL2 (macrophage inflammatory protein-2), and CXCL1 (keratinocyte-derived chemokine). There were dramatic increases in the recruitment of myosin heavy chain (MHC) II IA/IE(int)CD11c(int) cells, exudative macrophages, and dendritic cells in Ccl2 transgenic mouse lungs both at baseline and after bleomycin treatment compared with levels in wild-type mice. We further demonstrated that MHCII IA/IE(int)CD11c(int) cells engulfed apoptotic cells during acute lung injury. Our data suggested a previously undiscovered role for MHCII IA/IE(int)CD11c(int) cells in apoptotic cell clearance and inflammation resolution.
authors.affiliation: Division of Pulmonary,Department of Medicine, Duke Univ. School of Medicine, Durham, NC 27710, USA.
authors.forename: Jiurong
authors.initials: J
authors.lastname: Liang
authors.forename: Yoosun
authors.initials: Y
authors.lastname: Jung
authors.forename: Robert M
authors.initials: RM
authors.lastname: Tighe
authors.forename: Ting
authors.initials: T
authors.lastname: Xie
authors.forename: Ningshan
authors.initials: N
authors.lastname: Liu
authors.forename: Maura
authors.initials: M
authors.lastname: Leonard
authors.forename: Michael Dee
authors.initials: MD
authors.lastname: Gunn
authors.forename: Dianhua
authors.initials: D
authors.lastname: Jiang
authors.forename: Paul W
authors.initials: PW
authors.lastname: Noble
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D017209:Apoptosis; D001761:Bleomycin; D039521:CD11c Antigen / Q000378:metabolism; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D019169:Jurkat Cells; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008264:Macrophages / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018995:Myosin Heavy Chains / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology; D010587:Phagocytosis; D054390:Receptors, CCR2 / Q000172:deficiency / Q000235:genetics; D015854:Up-Regulation
chemical_list: D039521:CD11c Antigen; C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D018836:Inflammation Mediators; D054390:Receptors, CCR2; D001761:Bleomycin; D018995:Myosin Heavy Chains