Impaired Phagocytosis in Caveolin-1 Deficient Macrophages

Abstract

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.

Francisella Targets Cholesterol-Rich Host Cell Membrane Domains for Entry into Macrophages

“…Caveolae as specialized lipid raft domains, which are transformed into cuplike structure through the multimerization of the hairpinlike structure of caveolin, have been implicated in endocytic processes in phagocytic and nonphagocytic cells. It has also become clear that caveolin-1 is a necessary component for phagocytosis of parasites and bacteria as a first line of defense (66,67). It is not clear from the current state of research whether caveolin mediates phagocytosis or whether it is involved in supportive functions, such as membrane recruitment or signal transduction.…”

Kainic acid induces expression of caveolin-1 in activated microglia in rat brain

“…Such anti-inflammatory effects of caveolin-1 have partly been ascribed more directly to the action of caveolin-1 in macrophages. For example, caveolin-1 deficient macrophages display impaired phagocytosis [19]. Wang et al [20] demonstrated that caveolin-1 acts as a potent immunomodulatory effecter molecule in murine alveolar and peritoneal macrophages.…”

Cyclin and Caveolin Expression in an Acute Model of Murine Chagasic Myocarditis

“…35 Caveolae and caveola coat proteins, (caveolins,) are putatively implicated in many cellular processes, including trascytosis of macromolecules, cholesterol transport and signal transduction. 36 Recent insights into the physiological and pathopysiological roles of these organelles and the caveolins from genetically modified mice suggest that they may be profoundly important for post natal cardiovascular function, including endothelial barrier function, regulation of nitric oxide synthesis, cholesterol metabolism and cardiac function.…”