TY - JOUR
T1 - Pristane-Induced granulocyte recruitment promotes phenotypic conversion of macrophages and protects against diffuse pulmonary hemorrhage in Mac-1 deficiency
AU - Shi, Yiqin
AU - Tsuboi, Naotake
AU - Furuhashi, Kazuhiro
AU - Du, Qiuna
AU - Horinouchi, Asuka
AU - Maeda, Kayaho
AU - Kosugi, Tomoki
AU - Matsuo, Seiichi
AU - Maruyama, Shoichi
N1 - Publisher Copyright:
© 2014 by The American Association of Immunologists, Inc.
Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 2014/11/15
Y1 - 2014/11/15
N2 - Diffuse pulmonary hemorrhage (DPH) is an uncommon but critical complication of systemic lupus erythematosus. Peritoneal administration of 2,6,10,14-Tetramethylpentadecane (pristane) can recapitulate a lupus-like syndrome in mice, which can develop into DPH within a few weeks, especially in C57BL/6 mice. Mac-1 (CD11b/CD18), a leukocyte adhesion molecule, is known to play a role in inflammation by regulating migration of leukocytes into injured tissue. In this study, we aimed to clarify the role of Mac-1 in pristane-induced DPH, using Mac-1-/- and wild-Type (WT) mice on a C57BL/6 background. After pristane injection, Mac-1-/- mice showed reduced prevalence of DPH and attenuated peritonitis compared with WT mice. Analysis of the peritoneal lavage on days 5 and 10 after pristane treatment revealed increased numbers of eosinophils and alternatively activated macrophages, but decreased numbers of neutrophils and classically activated macrophages in Mac-1-/- mice compared with WT. Enhanced production of IL-4 and IL-13, both key mediators of macrophage polarization toward the mannose receptor+ (MMR+) phenotype, was observed in the peritoneal cavity of Mac-1-/- mice. Depletion of neutrophils and eosinophils or adoptive transfer of classically activated macrophages resulted in the exacerbation of pristane-mediated DPH in both WT and Mac-1-/- mice. Moreover, peritoneal transfer of F4/80high MMR+ alternatively activated macrophages successfully reduced the prevalence of DPH in WT mice. Collectively, Mac-1 promoted acute inflammatory responses in the peritoneal cavity and the lungs by downregulating granulocyte migration and subsequent phenotypic conversion of macrophages in a pristane-induced systemic lupus erythematosus model.
AB - Diffuse pulmonary hemorrhage (DPH) is an uncommon but critical complication of systemic lupus erythematosus. Peritoneal administration of 2,6,10,14-Tetramethylpentadecane (pristane) can recapitulate a lupus-like syndrome in mice, which can develop into DPH within a few weeks, especially in C57BL/6 mice. Mac-1 (CD11b/CD18), a leukocyte adhesion molecule, is known to play a role in inflammation by regulating migration of leukocytes into injured tissue. In this study, we aimed to clarify the role of Mac-1 in pristane-induced DPH, using Mac-1-/- and wild-Type (WT) mice on a C57BL/6 background. After pristane injection, Mac-1-/- mice showed reduced prevalence of DPH and attenuated peritonitis compared with WT mice. Analysis of the peritoneal lavage on days 5 and 10 after pristane treatment revealed increased numbers of eosinophils and alternatively activated macrophages, but decreased numbers of neutrophils and classically activated macrophages in Mac-1-/- mice compared with WT. Enhanced production of IL-4 and IL-13, both key mediators of macrophage polarization toward the mannose receptor+ (MMR+) phenotype, was observed in the peritoneal cavity of Mac-1-/- mice. Depletion of neutrophils and eosinophils or adoptive transfer of classically activated macrophages resulted in the exacerbation of pristane-mediated DPH in both WT and Mac-1-/- mice. Moreover, peritoneal transfer of F4/80high MMR+ alternatively activated macrophages successfully reduced the prevalence of DPH in WT mice. Collectively, Mac-1 promoted acute inflammatory responses in the peritoneal cavity and the lungs by downregulating granulocyte migration and subsequent phenotypic conversion of macrophages in a pristane-induced systemic lupus erythematosus model.
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U2 - 10.4049/jimmunol.1401051
DO - 10.4049/jimmunol.1401051
M3 - Article
C2 - 25281714
AN - SCOPUS:84910132234
VL - 193
SP - 5129
EP - 5139
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 10
ER -