Splenectomy predisposes to fungal sepsis through defective phagosome formation

Postsplenectomy septic sequelae may he fatal, but the mechanisms are unclear. We hypothesized that peritoneal macrophage (PMø) 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 (10⁷ 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, PMø were harvested and studied for their antifungal activity, including percentage PMø ingestion of C. albicans and vacuolar sealing of C. albicans within PMø, percentage C. albicans killing, and superoxide anion (O^-₂) 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 O^-₂ 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 O^-₂ release in response to candida. This descrepency between decreased killing and increased O^-₂ may result from increased leakage of O^-₂ from more unsealed vacuoles in the L + S group. Thus, L + S may predispose to candidainduced mortality through defective PMø intracellular candida killing while enhancing the release of O^-₂ extracellularly from unsealed vacuoles, causing tissue injury.