Human mast cell migration in response to members of the transforming growth factor-beta family.
Mast cells are known to accumulate at sites of inflammation, however, the chemotaxins involved remain largely undefined. Transforming growth factor-beta (TGF-beta) isoforms regulate numerous cellular functions, including cell growth and differentiation, formation of extracellular matrix, and the immune response. In this study we have compared the potency of different members of the TGF-beta family as human mast cell chemotaxins, and analyzed the expression of TGF-beta binding proteins on human mast cells. We were able to demonstrate that the maximal chemotactic response was attained at approximately 40 fM for the three TGF-beta isoforms, with TGF-beta3 being more effective than TGF-beta1 and TGF-beta2 at this concentration. This effect was observed in both the HMC-1 human mast cell line and in cultured primary mast cells. In addition, TGF-beta1, TGF-beta2, and less efficiently, TGF-beta3 inhibited the proliferation of HMC-1 cells. The migratory response is probably mediated through interaction with the TGF-beta serine/threonine type I and II receptors that were found to be expressed on the cells. No expression of TGF-beta type III receptor, endoglin, or the endothelial TGF-beta type I receptor ALK-1 could be detected. These results provide evidence that TGF-beta isoforms are highly potent chemotaxins for human mast cells and can play an important role in the recruitment of mast cells in inflammatory reactions.
Olsson
N
N
Department of Genetics and Pathology, Uppsala University, Sweden.
Piek
E
E
ten Dijke
P
P
Nilsson
G
G
D030201:Activin Receptors, Type I; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects*; D003432:Cross-Linking Reagents; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D006801:Humans; D008407:Mast Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D011233:Precipitin Tests; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000737:chemistry / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*
D000906:Antibodies; D003432:Cross-Linking Reagents; D020033:Protein Isoforms; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II