Identification of a mannoprotein fraction from Candida albicans that enhances human polymorphonuclear leukocyte (PMNL) functions and stimulates lactoferrin in PMNL inhibition of candidal growth.
Mannoprotein fractions of Candida albicans were assayed for their effects on the anticandidal activity of human polymorphonuclear leukocytes (PMNL). One fraction, MP-F2, enhanced PMNL inhibition of candidal growth in vitro as potently as bacterial lipopolysaccharide (LPS), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin-8. MP-F2-mediated PMNL activation was manifested on yeast and mycelial forms of the fungus, required the integrity of the mannan, and was due to an increase in the actual number of phagocytic PMNL rather than to a greater ingestion of fungal cells by each individual neutrophil. While not inducing augmented O2 production or degranulation of azurophilic granules, MP-F2 strongly stimulated the release of lactoferrin. Lactoferrin inhibited candidal growth in the absence of PMNL, and anti-lactoferrin antibodies reversed both this inhibition and the PMNL activation by MP-F2, GM-CSF, and LPS. Thus, PMNL may be activated by relevant candidal mannoproteins, and release of lactoferrin may add to other antimicrobial mechanisms of PMNL for the control of candidal infections.
Palma
C
C
Department of Medical Microbiology and Immunology, University of South Florida College of Medicine, Tampa 33612.
Serbousek
D
D
Torosantucci
A
A
Cassone
A
A
Djeu
J Y
JY
D000906:Antibodies / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development* / Q000302:isolation & purification; D010450:Endopeptidases; D016650:Fluorescein-5-isothiocyanate; D005656:Fungal Proteins / Q000302:isolation & purification / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D007781:Lactoferrin / Q000276:immunology / Q000494:pharmacology*; D008361:Mannosidases; D008562:Membrane Glycoproteins / Q000302:isolation & purification / Q000494:pharmacology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology*; D010587:Phagocytosis / Q000187:drug effects*; D013997:Time Factors; D014168:Transferrin / Q000494:pharmacology; D043323:alpha-Mannosidase
D000906:Antibodies; D005656:Fungal Proteins; D008562:Membrane Glycoproteins; D014168:Transferrin; C025363:mannoproteins; D009240:N-Formylmethionine Leucyl-Phenylalanine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D008361:Mannosidases; D043323:alpha-Mannosidase; D010450:Endopeptidases; D007781:Lactoferrin; D016650:Fluorescein-5-isothiocyanate