Regulation of integrin-dependent release in human lung mast cells and basophils.
The interaction of cells with surfaces or components of the extracellular matrix alters cell responses and is regulated by integrins on the cell surface. We have used monoclonal antibodies to CD29 and CD49d followed by an F(ab)2 fragment of rabbit anti-mouse IgG1 to cross-link the integrins on the surface of human lung mast cells and basophils. We found that cross-linking either CD29 or CD49d failed to initiate mediator release from the basophils of non-atopic and atopic donors [histamine release (HR) = 1 +/- 0.5% for CD29 and 1 +/- 0.5% for CD49d, n = 10, NS]. In contrast we found that clustering CD29 caused significant HR from the basophils of asthmatic donors (HR = 21 +/- 5%, n = 10, p < 0.005). Clustering of CD49d also caused significant degranulation in the same donors (HR = 9 +/- 3%, n = 10, p < 0.11). Incubating the basophils of these asthmatic donors with a synthetic RGD peptide significantly reduced CD29- and CD49d-induced histamine release. CS-1 peptide was also found to inhibit CD29-induced histamine release but had no significant effect on CD49d-induced histamine release. The tyrosine kinase inhibitors, genistein and piceatannol, completely ablated CD29- and CD49d-induced degranulation. In summary, we have shown that cross-linking integrins can initiate mediator release from the basophils of asthmatic patients and that this appears to involve recognition of RGD and activation of tyrosine kinase.
Warner
J A
JA
Department of Physiology and Pharmacology, University of Southampton, UK.
Goldring
K
K
Thomas
L H
LH
Lavens
S E
SE
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology*; D001249:Asthma / Q000276:immunology / Q000473:pathology; D001491:Basophils / Q000378:metabolism*; D002352:Carrier Proteins / Q000494:pharmacology; D005353:Fibronectins / Q000378:metabolism; D019833:Genistein; D006636:Histamine Release / Q000187:drug effects / Q000502:physiology; D006801:Humans; D039441:Integrin alpha4; D019012:Integrin beta1; D016023:Integrins / Q000276:immunology / Q000502:physiology*; D007529:Isoflavones / Q000494:pharmacology; D008168:Lung / Q000166:cytology*; D008407:Mast Cells / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011940:Receptor Aggregation / Q000187:drug effects / Q000502:physiology; D013267:Stilbenes / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D002352:Carrier Proteins; D005353:Fibronectins; D019012:Integrin beta1; D016023:Integrins; D007529:Isoflavones; D009842:Oligopeptides; D013267:Stilbenes; C094697:glutamyl-isoleucyl-leucyl-aspartyl-valine; D039441:Integrin alpha4; C041525:3,3',4,5'-tetrahydroxystilbene; C047981:arginyl-glycyl-aspartic acid; D019833:Genistein; D011505:Protein-Tyrosine Kinases