Evidence that protein kinase C regulates allosensitized T lymphocyte function.
The role of second messengers in the response of alloactivated T cells to growth factors (e.g., interleukin-2) is unknown. We have previously found that intracellular calcium may be an important T-cell alloactivation marker. To determine whether protein kinase C (PKC) is also involved in allosensitized T cell function, we studied the effects of the PKC agonists phorbol 12-myristate 13-acetate (PMA), mezerein (MEZ), and 1-oleoyl-2-acetylglycerol (OAG) and the PKC antagonists phloretin and D-sphingosine on the in vitro proliferation and migration of allosensitized cells from a C57BL/6 anti-DBA/2J mixed leukocyte culture (MLC). At 0.01-1.0 microgram/ml, PMA, a potent stimulant of PKC, exerted profound stimulatory effects on secondary MLC supernatant (2 degrees SN)-induced proliferation of allosensitized T cells (132-200% increase, P less than 0.01). Both MEZ and OAG are less potent activators of PKC than PMA but also stimulated T cell proliferation (132-152% of control, P less than 0.01). The PKC antagonists phloretin and D-sphingosine both inhibited proliferation by greater than 50% at 1.0-10.0 microM (P less than 0.01). Further experiments showed that these agents exert similar effects on in vitro T cell locomotion in a Boyden chamber assay. These data indicate that PKC activation may be an important component of allosensitized T cell proliferation and locomotion and may constitute a pathway by which T cell function may be modified in the allograft response.
Jordan
M L
ML
Department of Surgery, University of Pittsburgh, School of Medicine, Pennsylvania 15213.
Wright
J
J
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004075:Diglycerides / Q000494:pharmacology; D004224:Diterpenes; D005260:Female; D007114:Immunization; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D013729:Terpenes / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004075:Diglycerides; D004224:Diterpenes; D013729:Terpenes; C011309:mezerein; C038237:1-oleoyl-2-acetylglycerol; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate