TY - JOUR
T1 - Gamma interferon protects endothelial cells from damage by Candida albicans by inhibiting endothelial cell phagocytosis
AU - Fratti, Rutilio A.
AU - Ghannoum, Mahmoud A.
AU - Edwards, John E.
AU - Filler, Scott G.
PY - 1996
Y1 - 1996
N2 - Once Candida albicans comes in contact with endothelial cells, it induces cellular injury. This endothelial cell injury may be a mechanism by which blood-borne organisms escape from the intravascular compartment and invade the tissue parenchyma during hematogenous infection. We have been investigating the ability of cytokines to modulate endothelial cell injury caused by C. albicans. Previously we reported that pretreatment of endothelial cells with gamma interferon (IFN-γ) protects these cells from candidal injury in vitro. In the current study, we examined potential mechanisms of the cytoprotective effects of IFN-γ. Time course experiments demonstrated that maximal reduction in candidal injury of endothelial cells occurred after the endothelial cells had been exposed to IFN-γ for at least 72 h. In other studies, we determined that IFN-γ 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 required for damage to occur, inhibition of phagocytosis is likely a mechanism by which IFN-γ protects endothelial cells from candidal injury. We also found that the cytoprotective effect of IFN-γ is not mediated by reducing access of the organisms to intracellular endothelial cell iron or by upregulating the synthesis of reactive oxygen intermediates (which could potentially reduce the ability of C. albicans to injure endothelial cells). Thus, inhibiting endothelial cell phagocytosis of C. albicans may be a mechanism by which IFN-γ augments the host defense against hematogenously disseminated candidal infections.
AB - Once Candida albicans comes in contact with endothelial cells, it induces cellular injury. This endothelial cell injury may be a mechanism by which blood-borne organisms escape from the intravascular compartment and invade the tissue parenchyma during hematogenous infection. We have been investigating the ability of cytokines to modulate endothelial cell injury caused by C. albicans. Previously we reported that pretreatment of endothelial cells with gamma interferon (IFN-γ) protects these cells from candidal injury in vitro. In the current study, we examined potential mechanisms of the cytoprotective effects of IFN-γ. Time course experiments demonstrated that maximal reduction in candidal injury of endothelial cells occurred after the endothelial cells had been exposed to IFN-γ for at least 72 h. In other studies, we determined that IFN-γ 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 required for damage to occur, inhibition of phagocytosis is likely a mechanism by which IFN-γ protects endothelial cells from candidal injury. We also found that the cytoprotective effect of IFN-γ is not mediated by reducing access of the organisms to intracellular endothelial cell iron or by upregulating the synthesis of reactive oxygen intermediates (which could potentially reduce the ability of C. albicans to injure endothelial cells). Thus, inhibiting endothelial cell phagocytosis of C. albicans may be a mechanism by which IFN-γ augments the host defense against hematogenously disseminated candidal infections.
UR - http://www.scopus.com/inward/record.url?scp=0029919377&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029919377&partnerID=8YFLogxK
U2 - 10.1128/iai.64.11.4714-4718.1996
DO - 10.1128/iai.64.11.4714-4718.1996
M3 - Article
C2 - 8890230
AN - SCOPUS:0029919377
SN - 0019-9567
VL - 64
SP - 4714
EP - 4718
JO - Infection and immunity
JF - Infection and immunity
IS - 11
ER -