CHEMOATTRACTANT CAPACITY OF BOMBESIN, GASTRIN-RELEASING PEPTIDE AND NEUROMEDIN-C IS MEDIATED THROUGH PKC ACTIVATION IN MURINE PERITONEAL LEUKOCYTES

Bombesin-like peptides have been recently shown to regulate immune functions. In the present work, we have studied their action as chemoattractants for murine peritoneal macrophages and lymphocytes. The results showed a significant increase in the number of cells that migrate when they are exposed to a gradient of bombesin, gastrin-releasing peptide (GRP) or neuromedin C (from 10(-8) to 10(-12) M). The most effective of the three neuropeptides studied was GRP, even more than formyl-Met-Leu-Phe peptide (FMLP), an established leukocyte chemoattractant. GRP action was mediated through specific cell receptors as it was significantly reduced in presence of a competitive and specific bombesin receptor antagonist. In the presence of retinal, a protein kinase C (PKC) inhibitor, the chemoattractant capacity of GRP was considerably reduced. In order to investigate further the mechanism of action involved in the GRP effect, we measured PKC activity. Peritoneal cells incubated with GRP experimented an increase in PKC activity to the same extent of that produced by the PKC activator phorbol myristate acetate (PMA). These data prove that bombesin-like peptides are potent chemoattractants for murine peritoneal macrophages and lymphocytes, and that their action is at least in part mediated through PKC activation.