EFFECT OF ENDOTHELIAL-CELLS ON PHAGOCYTE-MEDIATED ANTICRYPTOCOCCAL ACTIVITY

The anticryptococcal activity of peripheral blood polymorphonuclear le ukocytes (PMN) and monocytes was compared on plastic versus human umbi lical vein endothelial cell surfaces. Various amounts of PMN and monoc ytes were incubated on plastic or endothelial surfaces and then challe nged for 18 h with Cryptococcus neoformans. Both phagocyte populations exhibited significantly more anticryptococcal activity on an endothel ial cell monolayer than on plastic. Prestimulating the endothelial cel l monolayer with interleukin-1 augmented the antifungal activity of PM N but not that of monocytes. In the absence of phagocytes, endothelial cells lacked activity. Blocking antibodies directed against endotheli al adhesion molecules ICAM-1 and ELAM-1 did not affect PMN-mediated in hibition of fungal growth. Recombinant interleukin-1 and interleukin-8 (two cytokines secreted by endothelial cells) activated neutrophils f or modestly enhanced antifungal activity. However, supernatants derive d from endothelial cells, as well as neutralizing antibodies directed against the endothelial cell-derived cytokines interleukin-8 and granu locyte-macrophage colony-stimulating factor failed to augment PMN anti fungal activity. PMN viability after 18 h was diminished on plastic co mpared with endothelial surfaces. While the percentages of C. neoforma ns bound to neutrophils were similar on both surfaces, the patterns of binding were markedly different: on endothelial (but not plastic) sur faces, most cryptococci were surrounded by greater than five PMN. Thus , phagocyte-mediated inhibition of cryptococcal growth is enhanced on endothelial monolayers compared with plastic surfaces, possibly as a r esult of differences in phagocyte viability and patterns of binding. B olstering the activity of circulating phagocytes by stimulating endoth elial cells may be of relevance in the treatment of patients with or a t risk for cryptococcemia.