A peptide secreted by human alveolar macrophages releases neutrophil granule contents.
A monoclonal antibody was developed against an 8,000-kDa enzyme-releasing peptide (ERP) released from human alveolar macrophages. ERP was isolated on an immunoaffinity column containing the antibody bound to staphylococcal protein A-Sepharose. Release of ERP from the macrophages is not changed by plastic adherence, phagocytosis, calcium ionophore, or phorbol esters. The peptide was not antigenically similar to interferon-gamma, tumor necrosis factor, or interleukin 1 alpha or 1 beta. The release of constituents from azurophilic and specific granules was the main identified biologic function of ERP. ERP was a more effective secretagogue in the untreated neutrophils and f-met-leu-phe was more effective in the cytochalasin B-treated neutrophils. Absorption of ERP from macrophage-conditioned medium removed a small amount of the chemotactic activity; however, the immunopurified peptide was not chemotactic or chemokinetic for neutrophils, and at high concentrations, it suppressed base line chemokinesis. Treatment of washed macrophages with trypsin released active ERP of approximately the same m.w. of spontaneously secreted ERP. These studies showed that human alveolar macrophages release a peptide which is a secretagogue for human neutrophils under conditions which may be encountered in the lungs during certain disease states. Proteolytic enzymes which are free in the lungs may release the peptide and lead to the secretion of neutrophil enzymes.
MacArthur
C K
CK
Department of Biochemistry, University of Texas Health Center at Tyler 75710.
Miller
E J
EJ
Cohen
A B
AB
D000911:Antibodies, Monoclonal / Q000276:immunology; D002633:Chemotaxis / Q000187:drug effects; D003571:Cytochalasin B / Q000494:pharmacology; D003594:Cytoplasmic Granules / Q000378:metabolism; D005089:Exocytosis / Q000187:drug effects*; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology; D008264:Macrophages / Q000378:metabolism*; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010455:Peptides / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D011650:Pulmonary Alveoli / Q000473:pathology; D014357:Trypsin
D000911:Antibodies, Monoclonal; D010455:Peptides; D003571:Cytochalasin B; D009240:N-Formylmethionine Leucyl-Phenylalanine; D014357:Trypsin