Clara cell protein (CC-16) induces a phospholipase A2-mediated inhibition of fibroblast migration in vitro.
Clara cell protein (CC-16, also designated CC-10) is synthesized by the bronchiolar epithelium and has been suggested as an inhibitor of phospholipase A2 (PLA2) activity. Therefore, CC-16 is a candidate for controlling inflammatory events in the lung. Because CC-16 amounts and function may be altered in fibrosing lung diseases in which bronchiolar injury has been reported, it was measured in alveolar fluids and sera. Secretory PLA2 activity in alveolar fluids and the influence of CC-16 on platelet-derived growth factor-induced human fibroblast chemotaxis and cytosolic PLA2 activity were also explored. CC-16 content was decreased in alveolar fluids from idiopathic pulmonary fibrosis (IPF: 1.3 +/- 0.1 mg/L) and bleomycin lung (1.1 +/- 0.2 versus 2.1 +/- 0.2 mg/L in controls, p < 0.05), whereas there was a three- to ninefold increase in secretory PLA2 activity (p < 0.05 versus controls). CC-16 inhibited fibroblast chemotaxis in a dose-dependent manner (90% inhibition at 30 micrograms/ml CC-16). This inhibition was reversed by reducing CC-16. CC-16 was also able to lower fibroblastic cytosolic PLA2 activity by 50% in vitro. In summary, CC-16 is able to inhibit fibroblast chemotaxis in vitro by mechanisms that may be related to a blockage of cytosolic PLA2 activity. It can be postulated that CC-16 deficiency may contribute to fibroblast burden activity in fibrosing lung diseases.
Lesur
O
O
Unité de Recherche Pulmonaire, University of Sherbrooke, Quebec, Canada.
Bernard
A
A
Arsalane
K
K
Lauwerys
R
R
Bégin
R
R
Cantin
A
A
Lane
D
D
D000328:Adult; D001761:Bleomycin / Q000009:adverse effects; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002455:Cell Division; D002633:Chemotaxis; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010740:Phospholipases / Q000037:antagonists & inhibitors*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D054467:Phospholipases A2; D011506:Proteins / Q000494:pharmacology* / Q000502:physiology; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D014598:Uteroglobin
D011506:Proteins; C556389:SCGB1A1 protein, human; D001761:Bleomycin; D014598:Uteroglobin; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2