Mechanisms of host defense against Candida species. I. Phagocytosis by monocytes and monocyte-derived macrophages.
We studied the biochemical basis of phagocytosis of Candida albicans, a serious pathogen, and Candida parapsilosis, which is rarely pathogenic, by human monocytes (Mo) and monocyte-derived macrophages (MDM). Optimal phagocytosis of both species by Mo required the presence of extracellular Ca2+ and opsonization through both the classic and alternative complement pathways. Serum-opsonized Candida were ingested equally by Mo and MDM; unopsonized Candida were phagocytosed only by macrophages, and uptake began slowly. This opsonin-independent phagocytosis required Ca2+ and could be blocked by yeast mannan or mannose-BSA conjugate, suggesting a role for the mannose receptor. Opsonized Candida elicited a vigorous increase in the concentration of [Ca2+]i in Mo and MDM, but no Ca2+ transient was detected in MDM stimulated with unopsonized Candida. Pretreatment of MDM with ionomycin to increase [Ca2+]i had no effect on phagocytosis of unopsonized Candida. Addition of 5 mM EGTA completely inhibited changes in [Ca2+]i in Mo and MDM, suggesting that the Ca2+ transient induced by opsonized Candida is due to an influx of extracellular Ca2+. Differences in pathogenicity between the two Candida species could not be explained by differences in any aspect of phagocytosis. Uptake mediated by the macrophage mannose receptor could play a role in clearance of Candida under opsonin-poor conditions.
Maródi
L
L
Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia 19104.
Korchak
H M
HM
Johnston
R B
RB
D002118:Calcium / Q000502:physiology; D002175:Candida / Q000276:immunology* / Q000472:pathogenicity; D002177:Candidiasis / Q000276:immunology*; D002478:Cells, Cultured; D002688:Chitinases / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D015759:Ionomycin / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology*; D008351:Mannans / Q000494:pharmacology; D008358:Mannose / Q000494:pharmacology; D009000:Monocytes / Q000276:immunology*; D009895:Opsonin Proteins / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects
D008351:Mannans; D009895:Opsonin Proteins; D004533:Egtazic Acid; D015759:Ionomycin; D002688:Chitinases; D008358:Mannose; D002118:Calcium