Effects of gamma-interferon on human neutrophils: protection from deterioration on storage.

stimulating factor (GM-CSF), formylmethionyl-leucyl-phenylalanine (FMLP), opsonized zymosan, and lipopolysaccharide (LPS), as compared with cells comparably preincubated in the absence of IFN-y. The decline in the staphylocidal activity of the stored PMN was also prevented in part by IFN-y, as was the depressed adherence of PMN stimulated with phorbo1 myristate acetate (PMA), FMLP, TNF, GM-CSF, and LPS. This protective effect of IFN-y on PMN function was associated with the prolonged surface expression of the complement receptor three (CR3) *chain (CDllb), CR3 pchain (CD18). FcRll (CD32). and FcRlll (CD16), and the appearance -INTERFERON (IFN-y) is well recognized as a lymphoY kine that can convert macrophages to an activated form with an associated increase in their respiratory burst and cytotoxic activity. However, IFN-y also can modulate the activity of polymorphonuclear leukocytes (PMN). Thus, the preincubation of normal PMN with IFN-y has been reported to increase phagocytosis14 (however, see ref 5), respiratory burst a~tivity~,~-l~ (however, see refs 5, 14), protein synthesi~,~~J~ degranulati~n,~.~ chemotaxis,16 microbicidal activity,3,10,13,14,17,18 and antibody-dependent cellular cytotoxicity (ADCC).”J9-21 This modulation of PMN function is associated with the appearance of functional highaffinity Fc receptor (FcR) for monomeric IgG (FcRI, CD64)334,z and with an increase in the level of the cytochrome b heavy chain (gp91-phox) transcript.u,x IFN-y added in vitro=.% or administered to humans in viv0~,2~928 also partially (or completely) reversed the depressed PMN respiratory burst and microbicidal activity of some patients with chronic granulomatous disease (CGD), an effect that was associated with increased expression of the gp91-phox IFN-y also decreases the frequency of serious infections in CGD.29 It has been proposed that IFN-y treatment of normal PMN results in prolonged survival in a functionally active state.3 We report here on the effect of IFN-y on the function of stored PMN. Human PMN preincubated overnight with IFN-y were found to have increased metabolic and microbicidal activity, adherence properties, surface CR3 and Fc receptor density, and steady-state mRNA levels for a number of phagocyte oxidase (phoK) components and CR3 and Fc receptors, as compared pith PMN comparably preincubated in the absence of IFN-y.