IL-1β STIMULATION INDUCES PARACRINE REGULATION OF PMN FUNCTION AND APOPTOSIS

Abstract

Polymorphonuclear leukocytes (PMN) play a crucial role in the primary immunological defense against infectious agents. PMN activation and function is influenced in a paracrine manner by cyto-kines and bacterial products. While cell-cell communication has been demonstrated between PMN and other cell types, 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-1β influenced this effect. Conditioned medias (CM) were prepared by incubating PMN in HBSS ± IL-1β for 1–4 h. Incubation of fresh PMN in these conditioned medias had little or no effect on the expression of cell surface FcαR expression or oxidative metabolism. However, incubation of PMN in CM-IL1α, but not control CM, increased phagocytotic activity and suppressed apoptosis. Additionally, CM-IL 1α, but not control CM, slowed the changes in Mac-1 and CR1 cell surface expression that occurred in HBSS within 2 h of incubation. Finally, control CM down-regulated the cell surface expression of PSGL-1; an effect that was not observed with CM-IL1α. In conclusion, we demonstrate that PMN are able to communicate with and influence the immunological function of other PMN independent of cell-cell contact, and that this influence is regulated by cytokines such as IL-1β. The major impact of this paracrine regulation is to down-regulate PMN apoptosis with the potential for an upregulated inflammatory response.