Two different signalling pathways for the induction of immunoreactive beta-endorphin secretion by human peripheral blood mononuclear cells.
Lymphocytes are now recognized as an extrapituitary source of neuropeptides, such as the opioid peptide beta-endorphin. In the present paper the intracellular signalling pathways involved in regulation of the secretion of immunoreactive (ir) beta-endorphin by human peripheral blood mononuclear cells are described. Activation of protein kinase-C with a phorbol ester rapidly induces secretion of ir-beta-endorphin by T-cells as well as by the non-T cell fraction. Stimulation of protein kinase-A by the addition of (Bu)2cAMP to T-cells or non-T-cells can also induce the secretion of ir-beta-endorphin by these cells. Investigation of the effect of different mitogens or antigen on ir-beta-endorphin secretion by lymphocytes revealed that the nature of the stimulus determines the kinetics of the response and the responding cell type. Induction of ir-beta-endorphin secretion by T-cells after stimulation with a T-cell mitogen is relatively fast; it can be observed within 3 h. In contrast, the response of the non-T-cell fraction to, for example, stimulation with (Bu)2cAMP can only be observed after 18 h of culture. Evidence will be presented that the fast response is mediated via protein kinase-C activation. The response observed after 18 h can be mediated via protein kinase-C as well as protein kinase-A activation.
Kavelaars
A
A
Department of Pediatric Immunology, University Hospital for Children and Youth Het Wilhelmina Kinderziekenhuis, Utrecht, The Netherlands.
Ballieux
R E
RE
Heijnen
C J
CJ
D000906:Antibodies / Q000502:physiology; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D017252:CD3 Complex; D004789:Enzyme Activation; D006801:Humans; D007158:Immunologic Techniques; D007375:Interleukin-1 / Q000276:immunology; D009000:Monocytes / Q000378:metabolism*; D010835:Phytohemagglutinins / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015398:Signal Transduction / Q000502:physiology*; D001615:beta-Endorphin / Q000378:metabolism*
D000906:Antibodies; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D007375:Interleukin-1; D010835:Phytohemagglutinins; D047428:Protein Kinase Inhibitors; D011948:Receptors, Antigen, T-Cell; D001615:beta-Endorphin; D011494:Protein Kinases; D011493:Protein Kinase C