Role of Ca2+ in the regulation of hormone receptor exposure during lymphocyte activation.
Ca2+ is known to be required for mitogen-mediated lymphocyte activation. In order to further define the regulatory role of Ca2+, we have examined the activation events which occur following treatment with ionomycin (a Ca2+ ionophore), as compared to those occurring following concanavalin A (Con A) treatment of mouse splenic T-lymphocytes. Our results indicate that ionomycin and Con A induce the exposure of both interleukin-2 (IL-2) and insulin receptors on the surface of the lymphocytes within the first 5 min of treatment. The exposed insulin and IL-2 receptors have the following properties: (1) they consist of both high- and low-affinity receptors; and (2) they appear on the cell surface in small clusters (i.e., patches) or, occasionally, a large aggregate (i.e., cap). c-myc gene expression and DNA synthesis occur in both the ionomycin and Con A-treated lymphocytes when either IL-2 or insulin is present in the culture medium. Furthermore, the exposure of both hormone receptors can be inhibited by either EGTA (a Ca2+ chelator), bepridil (a Ca2+ channel blocker), W-7 (a calmodulin antagonist) or cytochalasin D (a microfilament inhibitor). Treatment with these inhibitors also blocks the expression of c-myc gene and DNA synthesis which occur at later times during IL-2 and insulin-induced activation of ionomycin- and Con A-treated lymphocytes. These findings suggest that a Ca2+ and calmodulin-mediated contractile system is involved in the exposure of certain hormone receptors which appear to be required for complete lymphocyte activation.
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Department of Cell Biology and Anatomy, School of Medicine, University of Miami, Florida 33101.
Fregien
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Bourguignon
G J
GJ
Bourguignon
L Y
LY
D000818:Animals; D015764:Bepridil; D002118:Calcium / Q000502:physiology*; D015638:Cytochalasin D; D003572:Cytochalasins / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D007152:Immunologic Capping / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D011759:Pyrrolidines / Q000494:pharmacology; D011972:Receptor, Insulin / Q000032:analysis* / Q000187:drug effects / Q000502:physiology; D015375:Receptors, Interleukin-2 / Q000032:analysis / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology; D013601:T-Lymphocytes / Q000378:metabolism
D003572:Cytochalasins; D011759:Pyrrolidines; D015375:Receptors, Interleukin-2; D013449:Sulfonamides; D015638:Cytochalasin D; D004533:Egtazic Acid; C017967:W 7; D015764:Bepridil; D011972:Receptor, Insulin; D002118:Calcium