DIFFERENTIAL-EFFECTS OF INTERLEUKIN-15 (IL-15) AND IL-2 ON HUMAN NEUTROPHILS - MODULATION OF PHAGOCYTOSIS, CYTOSKELETON REARRANGEMENT, GENE-EXPRESSION, AND APOPTOSIS BY IL-15

Human neutrophils have been shown recently to express both the beta an d the gamma chains of the interleukin-2 receptor (IL-2R). IL-15, a cyt okine that has recently been cloned and characterized, was found to sh are many of the biological functions of IL-2 and is known to mediate s ignals through IL-2R beta and IL-2R gamma. In recent studies, we obser ved that IL-2 exerts few effects on various neutrophil functions, but information on IL-15-neutrophil interactions is lacking. In this study , we observed that IL-15, in contrast to IL-2, induces important morph ological cell shape changes that are typical of activated neutrophils. Furthermore, phagocytosis of opsonized sheep red blood cells was sign ificantly increased by IL-15 but not by IL-2. However, similar to IL-2 , IL-15 did not modulate the oxidative burst response. Furthermore, we observed that de novo RNA synthesis is increased in neutrophils by IL -15 along with de novo protein synthesis, whereas no significant effec t of IL-2 was noted. Among the different proteins that were found to b e upregulated by IL-15, one was identified by microsequencing as the c ytoskeletal protein actin. Finally, we found that IL-15 delays apoptos is of neutrophils more efficiently than IL-2 when evaluated by both mi croscopic observations and flow cytometry procedures. Furthermore, thi s phenomenon was dose-dependent (10 to 500 ng/mL), and, at 500 ng/mL, IL-15 delayed apoptosis as strongly as granulocyte-macrophage colony-s timulating factor. This study is the first to show that IL-15 is a sig nificant neutrophil agonist. Moreover, in view of the differential eff ects of IL-15 and IL-2 on this cell type, our results support the exis tence of a specific IL-15R component(s) on human neutrophils. (C) 1996 by The American Society of Hematology.