Function associated with IL-2 receptor-beta on human neutrophils. Mechanism of activation of antifungal activity against Candida albicans by IL-2.

Abstract

Polymorphonuclear neutrophils (PMN) are essential components of the host defense system against a wide variety of pathogens. We report here the novel finding that freshly isolated human PMN constitutively express detectable surface levels of IL-2R beta, but not IL-2R alpha, as analyzed by flow cytometry. Northern blot analysis confirmed the constitutive expression of mRNA for IL-2R beta in PMN. Scatchard analysis using 125I-labeled IL-2 demonstrated the presence of approximately 600 intermediate binding IL-2R per PMN, with a dissociation constant of 1.1 x 10(-9) M, similar to that of IL-2 binding to YT-1 tumor cells that specifically express IL-2R beta. More importantly, PMN were able to respond functionally to IL-2 by enhanced growth-inhibitory activity against an opportunistic fungal pathogen, Candida albicans. IL-2 activation of antifungal activity was dose-dependent, with some functional activation detected at 1 U/ml of rIL-2 and maximal activation at 1000 U/ml. The action of IL-2 was rapid, with maximal PMN activation after 30-min incubation with IL-2. The IL-2 enhancement of antifungal activity could be blocked by a specific antibody against IL-2R beta, but not by anti-IL-2R alpha. Analysis of the mechanism of IL-2 activation of PMN indicated that oxidative metabolism, as measured by superoxide anion production, was not involved. Instead, PMN release of lactoferrin appeared to be responsible for the heightened activity against C. albicans in IL-2-treated PMN. Not only was lactoferrin detected in the supernatants of IL-2-treated PMN, but also the antifungal activity of PMN activated by IL-2 could be blocked in the presence of antilactoferrin. These results, taken together, indicate that normal PMN are capable of functionally responding to IL-2 via expression of the IL-2R beta chain.