THE IN-VITRO EFFECT OF HUMAN POLYMORPHONUCLEAR LEUKOCYTE AZUROPHIL GRANULE COMPONENTS ON NATURAL-KILLER-CELL CYTOTOXICITY

We previously demonstrated that human polymorphonuclear leukocyte (PMN ) secretions are capable of activating and inhibiting natural killer c ell (NK) cytotoxicity depending on the eliciting PMN stimulus. Serum-o psonized zymosan induced PMN to secrete substances that enhanced NK ac tivity in vitro. Serum-opsonized zymosan stimulates the release of PMN azurophil granules, which contain both human neutrophil peptides (HNP s) and neutral serine proteases (NSPs). When HNPs and NSPs were tested for their ability to activate NK cells in peripheral blood lymphocyte s, all but cathepsin G consistently enhanced cytotoxicity above contro l values. HNP-induced cytotoxicity was significantly enhanced within 1 2 h, peaking at approximately 24 h. Of the HNPs, HNP-1 was the most po tent activator, enhancing NK activity at 1.25 mu g/ml. Interleukin-2 a nd interferon-gamma were not involved in this activational process, as antibodies to interleukin-2 and interferon-gamma did not block activa tion by HNPs and NSPs, and interleukin-2 receptor expression was unalt ered after 24 h of incubation. Enzymatically inactivated elastase and cathepsin G produced equivalent activational effects to their active c ounterparts. Antisera to elastase and cathepsin G decreased but did no t eliminate NK activation over untreated peripheral blood lymphocytes. These data suggest that certain PMN azurophil granule components, inc luding HNPs and NSPs directly increase the cytotoxic activity of NK ce lls.