Il-1 beta stimulation induces paracrine regulation of PMN function and apoptosis

Polymorphonuclear leukocytes (PMN) play a crucial role in the primary immun ological defense against infectious agents. PMN activation and function is influenced in a paracrine manner by cytokines and bacterial products. While cell-cell communication has been demonstrated between PMN and other cell t ypes, little data is available addressing PMN-PMN communication. Therefore, the aim of this study was to determine whether PMN were able to affect PMN function in vitro in a cell-contact independent manner, and whether IL-1 b eta influenced this effect. Conditioned medias (CM) were prepared by incuba ting PMN in HBSS +/- IL-1 beta for 1-4 h. Incubation of fresh PMN in these conditioned medias had little or no effect on the expression of cell surfac e Fc gamma R expression or oxidative metabolism. However, incubation of PMN in CM-IL1 beta, but not control CM, increased phagocytotic activity and su ppressed apoptosis. Additionally, CM-IL1 beta, but not control CM, slowed t he changes in Mac-1 and CR1 cell surface expression that occurred in HBSS w ithin 2 h of incubation. Finally, control CM down-regulated the cell surfac e expression of PSGL-1; an effect that was not observed with CM-IL1 beta. I n conclusion, we demonstrate that PMN are able to communicate with and infl uence the immunological function of other PMN independent of cell-cell cont act, and that this influence is regulated by cytokines such as IL-1 beta, T he major impact of this paracrine regulation is to downregulate PMN apoptos is with the potential for an upregulated inflammatory response.