Splenectomy predisposes to fungal sepsis through defective phagosome formation.
Postsplenectomy septic sequelae may be fatal, but the mechanisms are unclear. We hypothesized that peritoneal macrophage (PM phi) antimicrobial function is abnormal following splenectomy and that this may predispose to increased mortality from the fungal pathogen Candida albicans. Study 1 (in vivo): female CD-1 mice were randomized into control (C), laparotomy (L), or laparotomy+splenectomy (L + S) and inoculated with C. albicans (10(7) organisms, ip) and were studied for mortality. Study 2 (in vitro): mice were randomized to C, L, or L + S groups. Twenty-four hours later, PM phi were harvested and studied for their antifungal activity, including percentage PM phi ingestion of C. albicans and vacuolar sealing of C. albicans within PM phi, percentage C. albicans killing, and superoxide anion (O2-) generation, the mechanism by which candida are killed. Results showed decreased phagocytosis and killing of C. albicans in the L + S group (P < 0.05 vs C) and reduced vacuolar sealing (P < 0.05 vs C) but significantly higher O2- release compared to that in other groups (P < 0.05). Mortality in the L + S group from C. albicans sepsis was significantly higher than that in the other groups (60% compared to 20% in the L group and 13% in C, P < 0.02). This may have resulted from L + S-induced defective phagocytosis of C. albicans and depressed C. albicans killing but increased O2- release in response to candida. This discrepancy between decreased killing and increased O2- may result from increased leakage of O2- from more unsealed vacuoles in the L + S group. Thus, L + S may predispose to candida-induced mortality through defective PM phi intracellular candida killing while enhancing the release of O2- extracellularly from unsealed vacuoles, causing tissue injury.
Department of Surgery, Beaumont Hospital, Dublin, Ireland.
J E
JE
McCarthy
H P
HP
Redmond
W
W
Watson
J R
JR
O'Donnell
D
D
Bouchier-Hayes
D000818:Animals; D002176:Candida albicans / Q000276:immunology; D002177:Candidiasis / Q000276:immunology*; D005260:Female; D051379:Mice; D010587:Phagocytosis; D010588:Phagosomes / Q000502:physiology*; D011183:Postoperative Complications; D013156:Splenectomy; D013481:Superoxides / Q000378:metabolism
D013481:Superoxides