1887

Abstract

is a Gram-positive, anaerobic bacterium that is the most common cause of gas gangrene (clostridial myonecrosis) in humans. produces a variety of extracellular toxins that are thought to be the major virulence factors of the organism. However, has recently been shown to have the ability to survive in a murine macrophage-like cell line, J774-33, even under aerobic conditions. In J774-33 cells, can escape the phagosome and gain access to the cytoplasm. Since the receptor that is used for phagocytosis can determine the fate of an intracellular bacterium, we used a variety of inhibitors of specific receptors to identify those used by J774-33 cells to phagocytose . It was found that the scavenger receptor and mannose receptor(s) were involved in the phagocytosis of . In the presence of complement, the complement receptor (CR3) was also involved in the binding and/or uptake of . Since the receptor inhibition studies indicated that the scavenger receptor played a major role in phagocytosis, binding studies were performed with a Chinese hamster ovary (CHO) cell line expressing the mouse SR-A receptor. The cell line expressing the SR-A receptor showed a significant increase in binding in comparison to the non-transfected CHO cells. In the absence of opsonizing antibodies, the Fc receptor was not used to phagocytose . Forcing the macrophages to use a specific receptor by using combinations of different receptor inhibitors led to only a slight increase in co-localization of intracellular with the late endosome-lysosome marker LAMP-1. Carbohydrate analysis of strain 13 extracellular polysaccharide confirmed the presence of mannose and negatively charged residues of glucuronic acid, which may provide the moieties that promote binding to the mannose and scavenger receptors, respectively.

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2003-06-01
2024-03-28
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