engleski

Macrophage response to apoptotic cells

Apoptotic cells play a major role in immune homeostasis. One of the defining features of apoptotic cells is their ability to act as potent anti-inflammatory agents. The prompt and efficient removal of apoptotic cells is thought to be important in preventing the loss of cellular integrity and the subsequent leakage of cellular contents, and for limiting the immune response to autoantigens that trigger autoimmunity. Apoptotic cells are rapidly cleared by professional phagocytes in a noninflammatory manner. Previous observations showed properties unique to the dying cell determine the mode and outcome of phagocytic clearance. To determine if the method of induction of apoptosis has important consequences on phagocyte activity, apoptotic Jurkat cells and apoptotic HeLa cells were compared in their ability to elicit phagocytosis and modulation of proinflammatory cytokine production following induction of apoptosis with different apoptosis inducing stimuli. Jurkat T cells rendered apoptotic with etoposide failed to suppress lipopolysaccharide-driven inflammatory cytokine secretion or, correspondingly, NF-κB dependent or TNF- α promoter-driven transcriptional activity in transfected RAW264.7 macrophages. In contrast, induction of apoptosis in either Jurkat cells or HeLa epithelial cells with actinomycin D resulted in diminution of proinflammatory signaling from RAW264.7 cells and bone marrow derived macrophages. Murine bone marrow-derived macrophages readily engulfed apoptotic Jurkat cells treated with etoposide and with actinomycin D and HeLa-Act D cells. The prophagocytic and anti-inflammatory properties of the apoptotic target were independent of the cell type as both Jurkat cells and HeLa cells stimulated macrophage responses.

Apoptotic cells; Macrophages; Actinomycin D; Etoposide

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