Beta 1 integrin-mediated T cell adhesion is regulated by calcium ionophores and endoplasmic reticulum Ca(2+)-ATPase inhibitors.
Treatment of T lymphoblasts with stimuli that mobilize [Ca2+]i, such as ionophores (ionomycin and A23187) and endoplasmic reticulum Ca(2+)-ATPase inhibitors (thapsigargin, 2,5-di-(tert.-butyl)-hydroquinone and cyclopiazonic acid), activated T cell binding to extracellular matrix (ECM) proteins. T lymphoblast adhesion to ECM proteins stimulated by ionomycin, thapsigargin, or PMA was inhibited by an anti-beta 1 integrin mAb (4B4), confirming the role of beta 1 integrins in regulated T cell-ECM interactions. Study of the alpha integrin subunit specificity of activated lymphoblast-fibronectin interactions demonstrated that alpha 5 beta 1 was the major integrin receptor regulating binding to fibronectin. These results indicate that intracellular Ca2+ mobilization plays a major contributory role in the activation of T cell beta 1 integrins.
Hartfield
P J
PJ
Professorial Unit, St. John's Institute of Dermatology, St. Thomas' Hospital, U.M.D.S., London, U.K.
Greaves
M W
MW
Camp
R D
RD
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003094:Collagen; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D005353:Fibronectins; D006801:Humans; D006873:Hydroquinones / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D019012:Integrin beta1; D016023:Integrins / Q000276:immunology / Q000502:physiology*; D015759:Ionomycin / Q000494:pharmacology*; D007797:Laminin; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D013729:Terpenes / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019284:Thapsigargin
D000911:Antibodies, Monoclonal; D000975:Antioxidants; D005353:Fibronectins; D006873:Hydroquinones; D007211:Indoles; D019012:Integrin beta1; D016023:Integrins; D007797:Laminin; D013729:Terpenes; C019359:2,5-di-tert-butylhydroquinone; D000001:Calcimycin; D015759:Ionomycin; D019284:Thapsigargin; D003094:Collagen; D000252:Calcium-Transporting ATPases; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; C000543:cyclopiazonic acid