title: Potential role of Clara cell protein, an endogenous phospholipase A2 inhibitor, in acute lung injury.
abstract: It is now recognized that epithelial cells lining airways and alveoli are capable of releasing various mediators, which have the potential to modulate local inflammatory reactions. The amount of the 16 kDa Clara cell protein (CC16), an inhibitor of phospholipase A2 activity produced by pulmonary epithelial cells, was measured by means of a sensitive immunoassay in the unconcentrated bronchoalveolar lavage fluid (BALF) of 13 control subjects, and in patients with acute lung injury (14 with the full-blown adult respiratory distress syndrome (ARDS); 21 after standard cardiopulmonary bypass surgery, a known risk factor for ARDS). The level of CC16 was compared with other markers of inflammation with a wide range of molecular weights: albumin (nephelometry); total protein (spectrophotometry); beta 2-microglobulin (latex immunoassay); cystatin C (latex immunoassay); alpha 1-antitrypsin (immunoradiometry), and lipocortin-1 (enzyme-linked immunosorbent assay (ELISA)). The Clara cell protein (CC16) was detectable in all BALF, and significantly higher levels of this protein were observed in BALF from patients with acute lung injury. Changes in BALF Clara cell protein levels differed from those of alpha 2-macroglobulin and the natural phospholipase inhibitor lipocortin-1. Alpha 2-macroglobulin levels were not significantly enhanced in patients at risk for ARDS, but were increased in patients with ARDS; whereas, lipocortin 1 levels were not elevated in either group. Pretreatment of patients at risk for ARDS with high dose methylprednisolone did not alter the amount of Clara cell protein recovered in BALF. The mean CC16 level in BALF from patients with ARDS who died was significantly lower than from those who survived. The data presented in this study suggest that pulmonary epithelial cells secrete a natural anti-inflammatory protein during acute lung injury, which might have a protective and immunosuppressive role.
authors.affiliation: Dept of Intensive Care Medicine, University Hospital of Antwerp, University of Antwerp (UIA), Belgium.
authors.forename: P G
authors.initials: PG
authors.lastname: Jorens
authors.forename: Y
authors.initials: Y
authors.lastname: Sibille
authors.forename: N J
authors.initials: NJ
authors.lastname: Goulding
authors.forename: F J
authors.initials: FJ
authors.lastname: van Overveld
authors.forename: A G
authors.initials: AG
authors.lastname: Herman
authors.forename: L
authors.initials: L
authors.lastname: Bossaert
authors.forename: W A
authors.initials: WA
authors.lastname: De Backer
authors.forename: R
authors.initials: R
authors.lastname: Lauwerys
authors.forename: R J
authors.initials: RJ
authors.lastname: Flower
authors.forename: A
authors.initials: A
authors.lastname: Bernard
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000032:analysis / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D011506:Proteins / Q000032:analysis / Q000378:metabolism*; D012128:Respiratory Distress Syndrome / Q000378:metabolism*; D014598:Uteroglobin
chemical_list: D015415:Biomarkers; D004791:Enzyme Inhibitors; D011506:Proteins; C556389:SCGB1A1 protein, human; D014598:Uteroglobin; D010741:Phospholipases A; D054467:Phospholipases A2