Pristane-induced granulocyte recruitment promotes phenotypic conversion of macrophages and protects against diffuse pulmonary hemorrhage in Mac-1 deficiency.

Abstract

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 F4/80(high)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.

• Authors: Yiqin Shi, Naotake Tsuboi, Kazuhiro Furuhashi, Qiuna Du, Asuka Horinouchi, Kayaho Maeda, Tomoki Kosugi, Seiichi Matsuo, Shoichi Maruyama
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 193 Issue 10 Pg. 5129-39 (Nov 15 2014) ISSN: 1550-6606 [Electronic] United States
• PMID: 25281714 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 by The American Association of Immunologists, Inc.

Chemical References

• Antigens, Differentiation
• Interleukin-13
• Macrophage-1 Antigen
• Terpenes
• monocyte-macrophage differentiation antigen
• Interleukin-4
• pristane

Topics

• Animals
• Antigens, Differentiation (genetics, immunology)
• Cell Movement
• Gene Deletion
• Gene Expression Regulation
• Granulocytes (cytology, immunology)
• Hemorrhage (chemically induced, genetics, immunology, pathology)
• Interleukin-13 (genetics, immunology)
• Interleukin-4 (genetics, immunology)
• Lung (immunology, pathology)
• Lupus Erythematosus, Systemic (chemically induced, genetics, immunology, pathology)
• Macrophage-1 Antigen (genetics, immunology)
• Macrophages (immunology, pathology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Peritoneal Cavity (pathology)
• Peritoneal Lavage
• Phenotype
• Severity of Illness Index
• Signal Transduction
• Terpenes