TRANSFORMING GROWTH-FACTOR-BETA-1 MEDIATES MAST-CELL CHEMOTAXIS

It remains unknown which factor(s) control mast cell recruitment in ch ronic immune reactions. Although TGF-beta has been shown to function a s a potent chemotactic factor for monocytes, fibroblasts, and neutroph ils, its effect on mast cells has not been previously determined. in t his study, TGF-beta 1 was shown to cause directed migration of culture d mouse mast cells at femtomolar concentrations, with a maximal chemot actic response observed at 25 fM. Moreover, chemotaxis to TGF-beta was also seen using freshly isolated rat peritoneal mast cells. Addition of neutralizing Ab to TGF-beta abrogated its chemotactic activity for both freshly isolated rat peritoneal mast cells and cultured mouse mas t cells, whereas an irrelevant species-matched control Ab had no effec t. Checkerboard analysis confirmed the mast cell chemotactic activity after exposure to concentration gradients of TGF-beta. Mast cells were observed to undergo rapid and extensive shape changes on exposure to TGF-beta, assuming a polarized morphology in preparation for migration . Other known mast cell chemoattractants including laminin, c-kit liga nd, and IL-3 were found to be considerably less potent on a molar basi s in inducing directed migration. Affinity cross-linking studies ident ified TGF-beta binding proteins with M(r) at 70 and 288 kDa, consisten t with types I and III TGF-beta receptors on the mast cells. In summar y, TGF-beta is the most potent chemoattractant described for mast cell s and conceivably relevant, because pathologic processes mediated by T GF-beta are often associated with mast cell accumulation.