Modulation of natural killer (NK) cells by autologous neutrophils and monocytes

Although natural killer (NK) cell activity is remarkably stable in healthy individuals, the number and cytotoxicity of the cells fluctuate in disease. In man, regulatory mechanisms are virtually unexplored but depressed NK cell function accompanies most chronic diseases. A suppressive role of monocytes/macrophages has been reported. Since neutrophils (PMN) and monocytes (M) often respond reciprocally to pathologic stimuli, experiments were designed to investigate whether increments in PMN and M per se could influence NK cell function. Peripheral blood NK cells obtained by Percoll gradient centrifugation were either cocultured with various concentrations of autologous PMN or M or they were exposed to diffusates of these granulocytes in Millipore chambers. The treated NK cells were washed and then mixed with melanoma target cells in various effector:target cell ratios. It was observed that PMN diffusates augmented cytotoxicity whereas monocyte diffusates decreased the killing function of NK cells markedly and in a dose dependent fashion (P less than 0.001). The stimulatory effect of PMN diffusates was heat labile and not attributable to interferon. The inhibitory effect of M diffusates was heat stable, not due to prostaglandins or lysozyme, and irreversible within 6 hr of observation. Binding of effector to target cells was enhanced by PMN-media, and significantly inhibited by monocyte diffusates . It is therefore possible that factors elaborated by neutrophils and monocytes in vivo could also influence NK cell function.