title: Molecular mechanisms of lymphocyte extravasation. III. The loss of lymphocyte extravasation potential induced by pertussis toxin is not mediated via the activation of protein kinase C.
abstract: The present study evaluated whether protein kinase C (PKC) activation was involved in the lymphocytosis promoting properties of pertussis toxin (Ptx). The exposure of mouse lymphocytes to phorbol esters (as a means to selectively activate PKC) caused a depression in their subsequent capacity to localize into lymph nodes and Peyer's patches in vivo. This pattern of inhibition was quite similar to that observed with lymphocytes treated with Ptx. The mechanisms responsible for the observed decreases in localization to lymphoid organs caused by these two agents, however, appeared to be distinct. Exposure of lymphocytes to PMA was followed by a time and dosage-dependent decrease in the surface density of MEL-14 defined homing receptors. Ptx-treated lymphocytes retained normal density of this homing receptor. Consequently, PMA-treated lymphocytes lost their capacity to bind to high-endothelial venules in in vitro lymph node binding assays while Ptx-treated cells retained normal high-endothelial venule binding potential. We conclude from this study that: 1) the activation of PKC in lymphocytes by PMA can alter their recirculation properties via mechanisms that diminish their expression of surface receptors which support extravasation into lymph node and mucosal lymphoid tissues, and 2) even though Ptx has been reported to elevate the rate of inositol phosphate turnover in lymphocytes, the loss of extravasation potential of Ptx-treated lymphocytes is not mediated via the modification of surface homing receptors as observed in cells exposed to the known PKC activator, PMA.
authors.affiliation: Department of Pathology, University of Utah Medical School, Salt Lake City 84132.
authors.forename: K
authors.initials: K
authors.lastname: Huang
authors.forename: S Y
authors.initials: SY
authors.lastname: Im
authors.forename: W E
authors.initials: WE
authors.lastname: Samlowski
authors.forename: R A
authors.initials: RA
authors.lastname: Daynes
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules; D002465:Cell Movement / Q000187:drug effects; D003877:Dermatitis, Contact / Q000209:etiology; D004139:Dinitrofluorobenzene / Q000494:pharmacology; D004729:Endothelium, Lymphatic / Q000502:physiology; D004789:Enzyme Activation; D007116:Immunization, Passive; D007422:Intestines; D007546:Isoquinolines / Q000494:pharmacology; D008198:Lymph Nodes; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D037342:Pertussis Toxin; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
chemical_list: D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D007546:Isoquinolines; D010879:Piperazines; D010566:Virulence Factors, Bordetella; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D004139:Dinitrofluorobenzene; D037342:Pertussis Toxin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate