title: Synthesis and secretion of high- and low-molecular-weight forms of the enzyme-releasing peptide (ERP) from the macrophage-like cell line THP-1.
abstract: Neutrophil enzymes have been implicated as a source of lung injury in patients with the adult respiratory distress syndrome (ARDS) and with emphysema. We studied a human alveolar macrophage-derived peptide messenger, the enzyme-releasing peptide (ERP), which causes neutrophils to secrete their enzymes. The secretion and synthesis of ERP was studied in human alveolar macrophages and in the macrophage-like cell lines THP-1, HL-60, and U937. All four cell types secrete an ERP-like peptide. THP-1 cells secrete a higher concentration of the peptide than do macrophages. The secretion of ERP by THP-1 is suppressed by the protein synthesis inhibitors actinomycin D and cycloheximide. While the macrophages secrete ERP, they do not synthesize it. These studies suggest that ERP is synthesized by an alveolar macrophage precursor and stored in the mature macrophage for later release. 12-O-tetradecanoylphorbol-13-acetate (TPA) suppresses ERP secretion by THP-1 cells, but it does not modify secretion in macrophages. Escherichia coli-derived lipopolysaccharide and dimethyl sulfoxide do not modify secretion in either cell type. The THP-1 cells secrete a high- and low-mass-ratio (Mr) form of ERP-like proteins. The low Mr but not the high Mr form stimulates neutrophils to secrete their granule enzymes. We conclude that human alveolar macrophages secrete ERP but do not synthesize it. It is likely that ERP is made by an alveolar macrophage precursor in a high Mr form that is cleaved prior to secretion by the macrophages.
authors.affiliation: University of Texas Health Center, Tyler 75710.
authors.forename: C
authors.initials: C
authors.lastname: MacArthur
authors.forename: L
authors.initials: L
authors.lastname: Gray
authors.forename: A B
authors.initials: AB
authors.lastname: Cohen
mesh_terms: D000911:Antibodies, Monoclonal; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D008970:Molecular Weight; D010452:Peptide Biosynthesis; D010455:Peptides / Q000235:genetics* / Q000276:immunology; D011650:Pulmonary Alveoli; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D010455:Peptides; D003609:Dactinomycin; D003513:Cycloheximide; D013755:Tetradecanoylphorbol Acetate