title: Influence of mechanical stretch on thrombin regulation by fetal mixed lung cells.
abstract: Respiratory distress syndrome (RDS) is characterized by intrapulmonary fibrin deposition, which can adversely affect surfactant function, and stimulate fibroblast proliferation, which may contribute to the development of bronchopulmonary dysplasia (BPD). We speculated that the premature lung may have impaired regulation of thrombin, thus making preterm infants susceptible to fibrin formation within the lung. Therefore, we studied the effect of stretch, which simulates fetal breathing movements (FBMs), on the generation and inhibition of a key hemostatic enzyme-thrombin-by rat fetal mixed lung cells (FMLCs). Our results showed that stretch induced glycosaminoglycan production with increased antithrombin activity due to an increase in the concentration of active chondroitin sulfate. Stretch downregulated secretion of tissue factor procoagulant activity, which may lead to decreased thrombin generation on the surface of FMLCs. Overall, stretch enhanced the local control of thrombin by FMLCs. These results suggest that premature infants, who will have experienced less FBM, may have impaired thrombin regulation. Impaired thrombin regulation likely contributes to increased fibrin deposition and, potentially, the development of BPD.
authors.affiliation: The MRC Group in Lung Development, Respiratory Research Division, and the Neonatal Research Division of The Hospital for Sick Children, Toronto; and the Departments of Pediatrics of the University of Toronto, Toronto, Canada.
authors.forename: A K
authors.initials: AK
authors.lastname: Chan
authors.forename: B
authors.initials: B
authors.lastname: Baranowski
authors.forename: L
authors.initials: L
authors.lastname: Berry
authors.forename: M
authors.initials: M
authors.lastname: Liu
authors.forename: B
authors.initials: B
authors.lastname: Rafii
authors.forename: M
authors.initials: M
authors.lastname: Post
authors.forename: H
authors.initials: H
authors.lastname: O'Brodovich
authors.forename: P
authors.initials: P
authors.lastname: Monagle
authors.forename: M
authors.initials: M
authors.lastname: Andrew
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002809:Chondroitin Sulfates / Q000494:pharmacology; D005333:Fetus / Q000502:physiology; D005337:Fibrin / Q000378:metabolism; D006025:Glycosaminoglycans / Q000032:analysis; D006801:Humans; D007231:Infant, Newborn; D008168:Lung / Q000196:embryology*; D011661:Pulmonary Stretch Receptors / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012119:Respiration / Q000502:physiology; D012127:Respiratory Distress Syndrome, Newborn / Q000503:physiopathology*; D013917:Thrombin / Q000502:physiology*; D013925:Thromboplastin / Q000378:metabolism
chemical_list: D006025:Glycosaminoglycans; D012333:RNA, Messenger; D005337:Fibrin; D002809:Chondroitin Sulfates; D013925:Thromboplastin; D013917:Thrombin