Transforming growth factor-beta 1 mediates mast cell chemotaxis.
It remains unknown which factor(s) control mast cell recruitment in chronic immune reactions. Although TGF-beta has been shown to function as a potent chemotactic factor for monocytes, fibroblasts, and neutrophils, its effect on mast cells has not been previously determined. In this study, TGF-beta 1 was shown to cause directed migration of cultured mouse mast cells at femtomolar concentrations, with a maximal chemotactic 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 mast cells, whereas an irrelevant species-matched control Ab had no effect. 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 ligand, and IL-3 were found to be considerably less potent on a molar basis in inducing directed migration. Affinity cross-linking studies identified TGF-beta binding proteins with M(r) at 70 and 288 kDa, consistent with types I and III TGF-beta receptors on the mast cells. In summary, TGF-beta is the most potent chemoattractant described for mast cells and conceivably relevant, because pathologic processes mediated by TGF-beta are often associated with mast cell accumulation.
Gruber
B L
BL
Department of Medicine, State University of New York, Stony Brook 11794.
Marchese
M J
MJ
Kew
R R
RR
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002630:Chemotactic Factors / Q000494:pharmacology; D002633:Chemotaxis / Q000276:immunology*; D005355:Fibrosis; D066298:In Vitro Techniques; D008407:Mast Cells / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D051379:Mice; D009389:Neovascularization, Pathologic / Q000209:etiology; D009500:Neutralization Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000494:pharmacology
D002630:Chemotactic Factors; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta