Role of macrophages in the development of arteritis in MRL strains of mice with a deficit in Fas-mediated apoptosis.
The lpr and gld genes have been shown to encode the Fas antigen deletion mutant and the Fas ligand (FasL) mutant, respectively. An MRL strain of mice bearing the gld gene was observed to spontaneously develop granulomatous arteritis, similar to that in mice bearing the lpr gene, indicating that arteritis in this strain is due to an inefficient Fas-FasL interaction resulting in an incapacity for Fas-mediated apoptosis. The arterial lesions in both strains were characterized by a remarkable perivascular accumulation of activated macrophages bearing Mac-2 antigen, following the infiltration of CD4+ cells, and this resulted in the destruction of the arterial wall. Almost all of these infiltrating cells were Fas-positive, as determined in MRL/gld mice. Macrophage colony-stimulating factor (M-CSF), which is present at increased levels in MRL/lpr mice, but not in MRL/Mp- +/+ (MRL/+) mice, induced the expression of Mac-2 antigen and Fas antigen on spleen adherent cells of MRL/+ mice. Moreover, continuous infusion of M-CSF into the peritoneal cavity of subcutis of MRL/+ mice induced the release of oxygen radicals of peritoneal macrophages or granuloma formation associated with the massive accumulation of Mac-2+ cells, respectively. These findings suggest that macrophages in these mice, which may be activated by M-CSF and may avoid Fas-mediated apoptosis, play a critical role as effector cells in the destruction of arterial wall.
Taniguchi
Y
Y
Department of Pathology, Tohoku University School of Medicine, Sendai, Japan.
Ito
M R
MR
Mori
S
S
Yonehara
S
S
Nose
M
M
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001167:Arteritis / Q000209:etiology* / Q000276:immunology* / Q000473:pathology; D005434:Flow Cytometry; D007150:Immunohistochemistry; D015918:Infusion Pumps, Implantable; D007279:Injections, Subcutaneous; D008262:Macrophage Activation; D016173:Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000473:pathology / Q000648:ultrastructure; D051379:Mice; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D019014:fas Receptor / Q000235:genetics* / Q000502:physiology*
D019014:fas Receptor; D016173:Macrophage Colony-Stimulating Factor