title: 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.affiliation: Department of Nephrology, Internal Medicine, Nagoya University Graduate School of Medicine, Showa-ku, Aichi, Nagoya 466-8550, Japan; and.
authors.forename: Yiqin
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Nephrology, Internal Medicine, Nagoya University Graduate School of Medicine, Showa-ku, Aichi, Nagoya 466-8550, Japan; and tsubotake05@med.nagoya-u.ac.jp.
authors.forename: Naotake
authors.initials: N
authors.lastname: Tsuboi
authors.affiliation: Department of Nephrology, Internal Medicine, Nagoya University Graduate School of Medicine, Showa-ku, Aichi, Nagoya 466-8550, Japan; and Department of Pathology, Center for Excellence in Vascular Biology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Furuhashi
authors.affiliation: Department of Nephrology, Internal Medicine, Nagoya University Graduate School of Medicine, Showa-ku, Aichi, Nagoya 466-8550, Japan; and.
authors.forename: Qiuna
authors.initials: Q
authors.lastname: Du
authors.affiliation: Department of Nephrology, Internal Medicine, Nagoya University Graduate School of Medicine, Showa-ku, Aichi, Nagoya 466-8550, Japan; and.
authors.forename: Asuka
authors.initials: A
authors.lastname: Horinouchi
authors.affiliation: Department of Nephrology, Internal Medicine, Nagoya University Graduate School of Medicine, Showa-ku, Aichi, Nagoya 466-8550, Japan; and.
authors.forename: Kayaho
authors.initials: K
authors.lastname: Maeda
authors.affiliation: Department of Nephrology, Internal Medicine, Nagoya University Graduate School of Medicine, Showa-ku, Aichi, Nagoya 466-8550, Japan; and.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kosugi
authors.affiliation: Department of Nephrology, Internal Medicine, Nagoya University Graduate School of Medicine, Showa-ku, Aichi, Nagoya 466-8550, Japan; and.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Matsuo
authors.affiliation: Department of Nephrology, Internal Medicine, Nagoya University Graduate School of Medicine, Showa-ku, Aichi, Nagoya 466-8550, Japan; and.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Maruyama
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000276:immunology; D002465:Cell Movement; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006098:Granulocytes / Q000166:cytology / Q000276:immunology*; D006470:Hemorrhage / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018793:Interleukin-13 / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016177:Macrophage-1 Antigen / Q000235:genetics / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010529:Peritoneal Cavity / Q000473:pathology; D010533:Peritoneal Lavage; D010641:Phenotype; D012720:Severity of Illness Index; D015398:Signal Transduction; D013729:Terpenes
chemical_list: D000943:Antigens, Differentiation; D018793:Interleukin-13; D016177:Macrophage-1 Antigen; D013729:Terpenes; C036763:monocyte-macrophage differentiation antigen; D015847:Interleukin-4; C009042:pristane