Receptor binding specificity and pulmonary gene expression of the neutrophil-activating peptide ENA-78.
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.
Bozic
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Ina Sue Perlmutter Laboratory, Department of Pediatrics, Children's Hospital, Boston, Massachusetts, USA.
Gerard
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Gerard
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D000818:Animals; D001483:Base Sequence; D001667:Binding, Competitive; D002460:Cell Line; D054360:Chemokine CXCL1; D054365:Chemokine CXCL5; D018925:Chemokines; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000378:metabolism; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D003550:Cystic Fibrosis / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D015870:Gene Expression; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8 / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000737:chemistry; D016177:Macrophage-1 Antigen / Q000096:biosynthesis; D051379:Mice; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism*; D023063:Receptors, Interleukin-8B; D015854:Up-Regulation
C475896:CXCL1 protein, Bos taurus; C475829:CXCL1 protein, human; C486263:CXCL5 protein, human; D054360:Chemokine CXCL1; D054365:Chemokine CXCL5; D018925:Chemokines; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C475895:Cxcl1 protein, mouse; D016207:Cytokines; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D016177:Macrophage-1 Antigen; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D023063:Receptors, Interleukin-8B; C074302:keratinocyte-derived chemokines