Functional activation of human neutrophils by recombinant monocyte- derived neutrophil chemotactic factor/IL-8

• Published in: The Journal of immunology (1950) Vol. 144; no. 6; pp. 2205 - 2210
• Main Authors: Djeu, JY, Matsushima, K, Oppenheim, JJ, Shiotsuki, K, Blanchard, DK
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 15.03.1990; American Association of Immunologists
• Subjects: Biological and medical sciences; Candida albicans - immunology; Cell Degranulation; Cells, Cultured; Chemotactic Factors - pharmacology; Colchicine - pharmacology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunity, Cellular - drug effects; Immunobiology; In Vitro Techniques; Interleukin-8; Interleukins - pharmacology; Myeloid cells: ontogeny, maturation, markers, receptors; N-Formylmethionine Leucyl-Phenylalanine - pharmacology; Neutrophils - physiology; Pertussis Toxin; Polynuclears; Recombinant Proteins; Superoxides - metabolism; Virulence Factors, Bordetella - pharmacology; Fungi; Candida albicans; Human; Monocyte; Cytokine; Activation; Fungi Imperfecti; Neutrophil; Recombinant protein; Chemotactic factor; Thallophyta
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.144.6.2205

Monocyte-derived neutrophil chemotactic factor (MDNCF)/IL-8, a novel cytokine, distinct from IL-1 and TNF was recently purified and cloned. This study was performed to investigate the biologic effect of recombinant MDNCF/IL-8 on human polymorphonuclear neutrophils (PMN) by assessment of their growth inhibitory activity against Candida albicans. The chemoattractant, FMLP was used as a positive control. We demonstrated that MDNCF/IL-8, similar to FMLP, effectively enhanced PMN-mediated anti-Candida activity. MDNCF/IL-8, from 1.0 to 1000 ng/mol, enhanced PMN-mediated anti-Candida activity, whereas FMLP was effective from 10(-10) to 10(-7) M. The optimal dose of MDNCF/IL-8 for PMN stimulation was 10 ng/ml which equalled the optimal chemoattractant dose. MDNCF/IL-8 itself, like FMLP, had no direct effect on Candida growth at any concentration and it stimulated antifungal activity only in PMN but not in monocytes. Interestingly, MDNCF/IL-8 failed to stimulate directly the production of superoxide from PMN or prime the respiratory burst of PMN exposed to FMLP. However, MDNCF/IL-8 was capable of releasing azurophilic enzymes from cytochalasin B-treated PMN into the extracellular space. Enhancement of PMN anti-Candida activity and release of azurophilic enzymes from PMN by MDNCF/IL-8 were inhibited in the presence of colchicine, which is a known inhibitor of degranulation. These results suggest that MDNCF/IL-8 induced antifungal action of PMN via oxygen-independent pathways. Furthermore, MDNCF/IL-8 induction of anti-Candida action by PMN was inhibited by pretreatment with Bordetella pertussis toxin, suggesting that enhancement of PMN antifungal activity by MDNCF/IL-8, as well as by FMLP, may be mediated by a GTP-binding protein.