Leukotriene D 4 potentiates fibronectin-induced migration of human lung fibroblasts

Abstract

Fibroblasts play an important role in the repair and remodeling processes following injury. Leukotriene D 4 (LTD 4) 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 LTD 4 on normal human lung fibroblasts (NHLF) chemotaxis induced by human plasma fibronectin (HFn) was investigated using the modified Boyden's chamber technique. LTD 4 potentiated NHLF chemotaxis to HFn in concentration-dependent manner. A specific cysteinyl leukotriene receptor type 1 antagonist, pranlukast inhibited this effect, indicating that LTD 4 affected cell migration via its specific receptor. The potentiating effect of LTD 4 on fibroblast chemotaxis was completely abolished by pertussis toxin (PTX), suggesting that LTD 4-induced effect was dependent on PTX-sensitive Gi/o signaling. These findings suggest that LTD 4 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.