Receptor binding specificity and pulmonary gene expression of the neutrophil-activating peptide ENA-78

• Published in: American journal of respiratory cell and molecular biology Vol. 14; no. 3; pp. 302 - 308
• Main Authors: Bozic, CR, Gerard, NP, Gerard, C
• Format: Journal Article
• Language: English
• Published: United States Am Thoracic Soc 01.03.1996; American Thoracic Society
• Subjects: Animals; Base Sequence; Binding, Competitive; Cell Line; Cercopithecus aethiops; Chemokine CXCL1; Chemokine CXCL5; Chemokines; Chemokines, CXC; Chemotactic Factors - metabolism; Cloning, Molecular; Cystic Fibrosis - immunology; Cytokines - metabolism; Gene Expression; Growth Substances - metabolism; Humans; Intercellular Signaling Peptides and Proteins; Interleukin-8 - analogs & derivatives; Interleukin-8 - genetics; Interleukin-8 - metabolism; Lung - chemistry; Macrophage-1 Antigen - biosynthesis; Mice; Molecular Sequence Data; Neutrophils - immunology; Neutrophils - metabolism; Receptors, Interleukin - genetics; Receptors, Interleukin - metabolism; Receptors, Interleukin-8B; RNA, Messenger - analysis; Up-Regulation
• DOI: 10.1165/ajrcmb.14.3.8845182
• ISSN: 1044-1549

Neutrophil-activating peptide ENA-78 is a novel chemotactic cytokine isolated from a human type II pulmonary epithelial cell line. It is a member of the chemokine family of proinflammatory polypeptides and exhibits structural homology to interleukin-8 (IL-8) and GROalpha. The immunohistochemical identification of ENA-78 in pulmonary alveolar leukocytes of bovine pneumonic lungs supports a role for ENA-78 in the pathogenesis of pulmonary inflammation. Although ENA-78 is able to stimulate polymorphonuclear neutrophils (PMN), neither its binding specificities nor its expression in human pulmonary disease states have been determined. 125I-labeled ENA-78 binds with high affinity to human PMN. Its actions on PMN appear to be mediated by the IL-8 type B receptor, to which it binds with a K(d) of 2.2 nM. Human IL-8, GROalpha, and murine KC compete with high affinity for 125I-ENA-78 binding to the human IL-8 type B receptor. In contrast, 125I-ENA-78 does not bind to the IL-8 type A receptor nor does it compete significantly for 125I-IL-8 binding to this same receptor. ENA-78 is a potent upregulator of Mac-1 cell surface expression. In addition, ENA-78 mRNA is detected in cystic fibrosis lung but is not detected in normal donor lung. Thus, ENA-78 mRNA levels appear to be increased in human pulmonary inflammation and its stimulatory activities on PMN appear to be a function mediated primarily by the IL-8 type B receptor.