GAMMA-INTERFERON PROTECTS ENDOTHELIAL-CELLS FROM DAMAGE BY CANDIDA-ALBICANS BY INHIBITING ENDOTHELIAL-CELL PHAGOCYTOSIS

Once Candida albicans comes in contact with endothelial cells, it indu ces cellular injury, This endothelial cell injury may be a mechanism b y which blood-borne organisms escape from the intravascular compartmen t and invade the tissue parenchyma during hematogenous infection. We h ave been investigating the ability of cytokines to modulate endothelia l cell injury caused by C. albicans, Previously we reported that pretr eatment of endothelial cells with gamma interferon (IFN-gamma) protect s these cells from candidal injury in vitro, In the current study, we examined potential mechanisms of the cytoprotective effects of IFN-gam ma, Time course experiments demonstrated that maximal reduction in can didal injury of endothelial cells occurred after the endothelial cells had been exposed to IFN-gamma for at least 72 h. In other studies, we determined that IFN-gamma reduced endothelial cell phagocytosis of C. albicans by 41.3% compared with that of untreated endothelial cells ( P < 0.01), Since endothelial cell phagocytosis of C. albicans is requi red for damage to occur, inhibition of phagocytosis is likely a mechan ism by which IFN-gamma protects endothelial cells from candidal injury , We also found that the cytoprotective effect of IFN-gamma is not med iated by reducing access of the organisms to intracellular endothelial cell iron or by upregulating the synthesis of reactive oxygen interme diates (which could potentially reduce the ability of C. albicans to i njure endothelial cells). Thus, inhibiting endothelial cell phagocytos is of C. albicans may be a mechanism by which IFN-gamma augments the h ost defense against hematogenously disseminated candidal infections.