RESPONSIVENESS OF HUMAN NEUTROPHILS TO INTERLEUKIN-4 - INDUCTION OF CYTOSKELETAL REARRANGEMENTS, DE-NOVO PROTEIN-SYNTHESIS AND DELAY OF APOPTOSIS

Interleukin-4 (IL-4) and IL-13 are cytokines that share many biologica l activities. We have previously demonstrated that IL-13 affects a num ber of neutrophil responses, and here we extend our observations to IL -4. We present, for the first time, direct evidence for the presence o f functional IL-4 receptors on human neutrophils. We report that IL-4 induces RNA synthesis in a concentration-dependent manner and, based o n observations of the induction of morphological cell shape changes an d spreading onto glass, we demonstrate that IL-4 activates neutrophil cytoskeletal rearrangements. We further show that IL-4 is a potent act ivator of de novo protein synthesis in neutrophils, and we identify by microsequencing one of these proteins as the cytoskeletal protein act in. We were also able to demonstrate for the first time that actin is cleaved into at least two fragments of similar to 30 kDa (pI 5.4) and similar to 25 kDa (pI 5.0) in neutrophils. Finally, we report that IL- 4 delays neutrophil apoptosis, as assessed by morphological observatio ns from cytocentrifuge preparations, as well as by measurement of diff erences in staining by flow cytometry with both propidium iodide and H oechst reagent. Taken together, we conclude that IL-4 is a more potent neutrophil agonist than previously believed. We discuss the possibili ty that the induction of the de nova synthesis of actin by IL-4 is rel ated to the mechanism by which this cytokine delays apoptosis; in addi tion, the cleavage of this protein is likely to contribute to the apop totic process.