title: Carboxypeptidase M activity is increased in bronchoalveolar lavage in human lung disease.
abstract: Carboxypeptidase M (CPM) cleaves the C-terminal arginine and lysine of peptides; it is expressed in the lung, especially on the plasma membrane of alveolar type I cells. Here, we report on CPM in human bronchoalveolar lavage (BAL) collected from 69 patients and analyzed for activity, cell number and type, and protein level. Seventy-six percent of CPM activity, measured at pH 7.5 with 5-dimethylamino-naphthalene-1-sulfonyl-alanyl-arginine (Dansyl-Ala-Arg) substrate, was immunoprecipitated with polyclonal antibody to purified human enzyme. In patients without active lung disease, CPM activity in BAL was 7.69 (+/- 2.12) nmol/h/mg protein, but in patients with acute pneumonia, it was 29.25 (+/- 4.06) (p < 0.01). In patients with Pneumocystis carinii pneumonia, CPM activity was elevated to 26.00 (+/- 4.85) (p < 0.01) and in patients with lung cancer, to 30.95 (+/- 4.12) (p < 0.01). The activity was not associated with the cellular elements of BAL. The highest specific activity was in the large aggregate fraction of surfactant, which also contained the highest concentration of phosphorus. Transmission electron microscopy of this fraction revealed the presence of typical lamellar bodies and tubular myelin structures. The high CPM activity may stem from its induction and release in acute lung disease. In addition, CPM may be a marker of infection with certain pathogens and an indicator of type I cell injury in parenchymal lung diseases.
authors.affiliation: Department of Pharmacology, University of Illinois College of Medicine, Chicago, USA.
authors.forename: T
authors.initials: T
authors.lastname: Dragović
authors.forename: D E
authors.initials: DE
authors.lastname: Schraufnagel
authors.forename: R P
authors.initials: RP
authors.lastname: Becker
authors.forename: M
authors.initials: M
authors.lastname: Sekosan
authors.forename: E G
authors.initials: EG
authors.lastname: Votta-Velis
authors.forename: E G
authors.initials: EG
authors.lastname: Erdös
mesh_terms: D000409:Alanine / Q000378:metabolism; D001120:Arginine / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry* / Q000166:cytology; D002452:Cell Count; D002462:Cell Membrane / Q000201:enzymology; D003619:Dansyl Compounds / Q000378:metabolism; D005260:Female; D058851:GPI-Linked Proteins; D006801:Humans; D002479:Inclusion Bodies / Q000648:ultrastructure; D008171:Lung Diseases / Q000201:enzymology* / Q000473:pathology; D008175:Lung Neoplasms / Q000201:enzymology / Q000473:pathology; D008297:Male; D008666:Metalloendopeptidases / Q000032:analysis*; D008854:Microscopy, Electron; D008875:Middle Aged; D009186:Myelin Sheath / Q000648:ultrastructure; D010758:Phosphorus / Q000032:analysis; D011014:Pneumonia / Q000201:enzymology / Q000473:pathology; D011020:Pneumonia, Pneumocystis / Q000201:enzymology / Q000473:pathology; D011233:Precipitin Tests; D011650:Pulmonary Alveoli / Q000201:enzymology / Q000473:pathology; D011663:Pulmonary Surfactants / Q000032:analysis
chemical_list: D003619:Dansyl Compounds; D058851:GPI-Linked Proteins; D011663:Pulmonary Surfactants; D010758:Phosphorus; D001120:Arginine; C058479:carboxypeptidase M; D008666:Metalloendopeptidases; D000409:Alanine