Impaired phagocytosis in caveolin-1 deficient macrophages.
Caveolae are plasma membrane invaginations that function as important regulators of numerous cellular processes, including signal transduction, cholesterol trafficking, and endocytosis. Caveolin-1 (Cav-1) constitutes the main structural protein of caveolae membranes. Here, we report an in vivo increase in the number of apoptotic cells in the thymus and spleen of Cav-1 deficient mice, following whole-body gamma-irradiation. We demonstrate that this increase in apoptotic cells is not due to increased apoptosis in lymphocytes per se, which normally do not express Cav-1, but rather to the decreased phagocytic clearance of apoptotic cells by macrophages, which do express Cav-1. Utilizing in vitro phagocytosis assays of both apoptotic thymocytes and Escherichia coli K-12 BioParticles, we demonstrate that the loss of Cav-1 decreases the phagocytic ability of thioglycollate-elicited peritoneal macrophages. We suggest that impaired macrophage phagocytosis in Cav-1 knockout mice could have implications for altered innate immunity against pathogens, the regulation of inflammatory responses, and the development of autoimmune disease.
Li
Jiangwei
J
Department of Molecular Pharmacology & Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Scherl
Alexis
A
Medina
Freddy
F
Frank
Philippe G
PG
Kitsis
Richard N
RN
Tanowitz
Herbert B
HB
Sotgia
Federica
F
Lisanti
Michael P
MP
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics / Q000473:pathology; D051242:Caveolin 1 / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*; D002478:Cells, Cultured; D007113:Immunity, Innate / Q000235:genetics; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010587:Phagocytosis / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000382:microbiology / Q000473:pathology
D051242:Caveolin 1