Regulatory effects of stem cell factor and interleukin-4 on adhesion of human mast cells to extracellular matrix proteins.
Mast cells are inflammatory and immunoregulatory cells resident in tissues. They develop from bone marrow-derived progenitor cells that enter the tissue through the blood circulation. The specific localization and migration of mast cells in tissues is dependent on their interaction with extracellular matrix (ECM) proteins. Adhesion of human mast cells isolated from intestinal mucosa and cultured in the presence of stem cell factor (SCF) to ECM proteins is analyzed. It was observed that SCF is a unique cytokine enhancing mast cell adhesion to all tested ECM proteins (fibronectin, laminin, collagen I, III, IV, VI, XIV) up to 5-fold, particularly to fibronectin (54% +/- 12% of mast cells) and to denatured collagens (40% +/- 12% on cyanogen bromide-cleaved peptides of collagen I). Most noteworthy, preculture of mast cells with interleukin-4 (IL-4), in addition to SCF, reduced their potency to adhere to ECM proteins to one third compared to mast cells cultured with SCF alone. Mast cell adhesion was preferentially mediated by beta1 integrins, and most cells expressed the ECM-binding integrins alpha2beta1, alpha3beta1, alpha4beta1, alpha5beta1, and alphaVbeta3. SCF-induced mast cell adhesion was totally blocked by wortmannin and apigenin, indicating an involvement of phosphatidylinositol 3-kinase and mitogen-activated protein kinase, and it was related to an up-regulation of the HUTS-21 beta1 epitope, which is associated with an activated conformation of beta1. In conclusion, these data indicate that SCF induces the adhesion of cultured mast cells to ECM proteins, whereas IL-4 may promote detachment from the ECM.
Lorentz
Axel
A
Department of Internal Medicine/Gastroenterology, Medical School of Hannover, D-30623 Hannover, Germany.
Schuppan
Detlef
D
Gebert
Andreas
A
Manns
Michael P
MP
Bischoff
Stephan C
SC
D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000378:metabolism; D007377:Interleukin-3 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology / Q000502:physiology*; D007413:Intestinal Mucosa / Q000166:cytology; D008407:Mast Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D019089:Stem Cell Factor / Q000494:pharmacology / Q000502:physiology*
D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D016023:Integrins; D007377:Interleukin-3; D019089:Stem Cell Factor; D015847:Interleukin-4