Increased gelsolin expression and retarded collagen lattice contraction with smooth muscle cells from Crohn's diseased intestine

Intestinal smooth muscle cells (SMC) produce the fibrotic tissue, stricture s, that characterize Crohn's disease. These SMC change their phenotype from a contractile muscle form to an inflammation-responsive form that migrates and synthesizes a collagen matrix. It is postulated that the inflammatory responsive SMC form associates differently with its surrounding collagen ma trix compared to the normal SMC form. SMC derived from Crohn's diseased and uninvolved bowel were sustained in cell culture. Cultured SMC incorporated in collagen lattices have the capacity to reduce the size of that lattice, referred to as lattice contraction. At day 2, Crohn's SMC-populated collag en lattices were reduced to 21% of their initial area, while non-Crohn's SM C collagen lattices were reduced to 8%. Crohn's SMC demonstrate retarded la ttice contraction compared to non-Crohn's SMC. When grown in monolayer cult ure, Crohn's-derived SMC cover 30% more area than non-Crohn's SMC. By Weste rn blot analysis Crohn's SMC express more gelsolin, an actin-binding protei n found elevated in cells exhibiting increased cell motility. Was the incre ased expression of gelsolin related to retarded collagen lattice contractio n! Intracellular levels of gelsolin were elevated by the electroporation of plasma gelsolin protein into suspended non-Crohn's SMC. When incorporated in collagen lattices, gelsolin loaded cells showed retarded lattice contrac tion compared to SMC loaded with albumin. Crohn's SMC show increased expres sion of gelsolin, which may be associated with a diminished capacity to reo rganize collagen fiber bundles. It is suggested that increased concentratio ns of gelsolin in Crohn's SMC is consistent with enhanced cell migration as a consequence of the inflammatory state of Crohn's diseased intestine. (C) 2000 Wiley-Liss, Inc.