STRUCTURE AND NEUTROPHIL-ACTIVATING PROPERTIES OF A NOVEL INFLAMMATORY PEPTIDE (ENA-78) WITH HOMOLOGY TO INTERLEUKIN-8

A new neutrophil-activating peptide, termed ENA-78, was identified in the conditioned media of stimulated human type II epithelial cell line A549. In response to stimulation with either interleukin 1-beta (IL-1-beta) or tumor necrosis factor-alpha (TNF-alpha), ENA-78 was produced and secreted concomitantly with IL-8, GRO-alpha, and GRO-gamma. ENA-78 consists of 78 amino acids (AGPAAAVLRELRCVCLQTTQGVHPKMISNLQVFAIGPQCSKVEVVASLKNGKEICLDPEAPFLKKVIQKILDGGNKEN) and has a molecular weight of 8,357. It has four cysteines positioned identically to those of II-8 and analogues, and thus belongs to the CXC family of peptides. ENA-78 is related to neutrophil-activating peptide 2 (NAP-2) and GRO-alpha (sequence identity, 53% and 52%, respectively) and IL-8 (22% identity). Like NAP-2 and GRO-alpha, ENA-78 stimulates neutrophils, inducing chemotaxis, a rise in intracellular free calcium and exocytosis. Cross-desensitization experiments indicate that ENA-78 acts through the same type of receptors as IL-8, NAP-2, and GRO-alpha.