Modulation of human airway smooth muscle migration by lipid mediators and Th-2 cytokines.

Cysteinyl leukotrienes and the T helper (Th)-2 cytokines IL-5 and IL-13 directly modulate human airway smooth muscle functions such as contraction and proliferation. We studied the effects of other lipid mediators involved in asthma pathophysiology such as prostaglandin D2 (PGD2), lipoxin, and isoprostanes, and the cytokines, IL-5, IL-4, and IL-13 on human airway smooth muscle cell migration. Chemotaxis and chemokinesis of cultured airway smooth muscle cells from humans without asthma (second to fifth passages, n = 6) were studied using collagen-I–coated polycarbonate membranes in Transwell culture plates. Receptor expression and kinase activation were studied by flow cytometry, polymerase chain reaction, and Western blotting techniques. In contrast to LTE4- stimulated (10−6 M) chemokinesis and LTE4-primed migration toward platelet-derived growth factor (PDGF), isoprostane 15-F2t-IsoP, and IL-5 were neither chemotactic nor chemokinetic. PGD2 (10−10–10−6 M) was a chemoattractant and primed migration toward...