Natural inhibitor from Candida albicans blocks release of azurophil and specific granule contents by chemotactic peptide-stimulated human neutrophils.
A product released by Candida albicans hyphae which was previously determined to block the neutrophil respiratory burst also inhibited the degranulation response elicited by the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP). When neutrophils were incubated with 100 micrograms of this Candida hyphal inhibitory product (CHIP) per ml and stimulated with 1,000 nM FMLP, release of the azurophil granule marker beta-glucuronidase and the specific granule marker lactoferrin was decreased to 31.2 +/- 5.7 and 35.7 +/- 5.3% of control, respectively. Inhibition was concentration dependent, with a half-maximal reduction of beta-glucuronidase and lactoferrin release being induced by 4 and 1 micrograms of CHIP per ml, respectively. In contrast to these striking alterations in response to FMLP, CHIP had no significant effect on lactoferrin release stimulated by phorbol myristate acetate. Moreover, actin polymerization, which has been suggested to be involved in regulation of degranulation, was unaffected by CHIP whether the neutrophils were stimulated by FMLP or phorbol myristate acetate. The selectivity of inhibition of neutrophil degranulation thus provides additional confirmation that CHIP is a useful agent for exploring human neutrophil activation pathways.
Smail
E H
EH
Department of Medicine, Boston University School of Medicine, Massachusetts 02118.
Kolotila
M P
MP
Ruggeri
R
R
Diamond
R D
RD
D008841:Actin Cytoskeleton / Q000502:physiology; D000199:Actins / Q000502:physiology; D002176:Candida albicans / Q000276:immunology*; D002470:Cell Survival; D005089:Exocytosis; D007111:Immunity, Cellular; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000037:antagonists & inhibitors; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors
D000199:Actins; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D013755:Tetradecanoylphorbol Acetate