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 altere...

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Published inAmerican journal of respiratory and critical care medicine Vol. 152; no. 1; p. 290
Main Authors Lesur, O, Bernard, A, Arsalane, K, Lauwerys, R, Bégin, R, Cantin, A, Lane, D
Format Journal Article
LanguageEnglish
Published United States 01.07.1995
Subjects
Adult
Bleomycin - adverse effects
Bronchoalveolar Lavage Fluid - chemistry
Cell Division
Chemotaxis
Female
Fibroblasts - cytology
Fibroblasts - physiology
Humans
Immunohistochemistry
Lung - drug effects
Lung - metabolism
Lung - pathology
Male
Middle Aged
Phospholipases - antagonists & inhibitors
Phospholipases A - antagonists & inhibitors
Phospholipases A - metabolism
Phospholipases A - physiology
Phospholipases A2
Proteins - pharmacology
Proteins - physiology
Pulmonary Fibrosis - chemically induced
Pulmonary Fibrosis - metabolism
Pulmonary Fibrosis - pathology
Uteroglobin
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Summary: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.
ISSN:1073-449X