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.

Directed Induction of Functional Multi-ciliated Cells in Proximal Airway Epithelial Spheroids from Human Pluripotent Stem Cells

“…We established a method of 3D differentiation without feeder cells to generate hPSC-derived PAEC spheroids via isolated progenitor cells using CPM as a surface antigen, which is reportedly a biomarker of lung diseases, such as acute pneumonia and lung cancer ( Dragović et al., 1995 ). It is noted that the inhibition of the Notch pathway induced not only MCACs but also PNECs from hPSCs, which is consistent with the studies of genetic murine models ( Tsao et al., 2009 , Morimoto et al., 2012 ).…”

Purification of a 68-kDa cysteine proteinase from crude extract of Pneumocystis carinii

“…Collagenase and serine proteinase activities were found in the bronchoalveolar lavage fluid of rats with PCP, which may lead to damage of the basal lamina and interstitial connective tissue and thereby can contribute to impaired alveolar function during PCP (Sukura et al, 1995). Carboxypeptidase M activity has been demonstrated to be elevated in the bronchoalveolar lavage fluid of patients with acute lung disease such as acute pneumonia, PCP, and lung cancer, which may be an indicator of type I cell injury in lung diseases (Dragovic et al, 1995). Other host factors are thought to be involved in the pathogenesis of PCP.…”

A Novel Alveolar Type I Cell–Specific Biochemical Marker of Human Acute Lung Injury

“…Although there have been many studies of other biochemical markers in acute lung injury (5), this study is the first to describe a marker known to be specific to the alveolar epithelial type I cell. Another molecule found in type I cells, carboxypeptidase M, was found to be increased in BAL obtained from patients with lung disease (27). Although carboxypeptidase M is found on the apical membrane of type I cells, it is also found in liver, heart, kidney and alveolar macrophages.…”