title: Leukotriene D4 potentiates fibronectin-induced migration of human lung fibroblasts.
abstract: Fibroblasts play an important role in the repair and remodeling processes following injury. Leukotriene D4 (LTD4) is a potent mediator in inflammatory processes, but the direct effect of cysteinyl leukotrienes on fibroblast migration remains unelucidated. In this study, the effect of the LTD4 on normal human lung fibroblasts (NHLF) chemotaxis induced by human plasma fibronectin (HFn) was investigated using the modified Boyden's chamber technique. LTD4 potentiated NHLF chemotaxis to HFn in concentration-dependent manner. A specific cysteinyl leukotriene receptor type 1 antagonist, pranlukast inhibited this effect, indicating that LTD4 affected cell migration via its specific receptor. The potentiating effect of LTD4 on fibroblast chemotaxis was completely abolished by pertussis toxin (PTX), suggesting that LTD4-induced effect was dependent on PTX-sensitive Gi/o signaling. These findings suggest that LTD4 has a potential to augment fibroblast chemotaxis, and to contribute to regulation of the wound healing and following remodeling in fibrotic processes of the lung.
authors.affiliation: The Department of Respiratory Medicine, University of Tokyo, Graduate School of Medicine, Tokyo, Japan. jkato-tky@umin.ac.jp
authors.forename: Jun
authors.initials: J
authors.lastname: Kato
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kohyama
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Okazaki
authors.forename: Masashi
authors.initials: M
authors.lastname: Desaki
authors.forename: Takahide
authors.initials: T
authors.lastname: Nagase
authors.forename: Stephen I
authors.initials: SI
authors.lastname: Rennard
authors.forename: Hajime
authors.initials: H
authors.lastname: Takizawa
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D002478:Cells, Cultured; D002633:Chemotaxis / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000502:physiology*; D005353:Fibronectins / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D017998:Leukotriene D4 / Q000502:physiology*; D008168:Lung / Q000166:cytology / Q000502:physiology; D037342:Pertussis Toxin / Q000494:pharmacology; D020298:U937 Cells
chemical_list: D000276:Adjuvants, Immunologic; D005353:Fibronectins; D017998:Leukotriene D4; D037342:Pertussis Toxin