Characterization of the phorbol 12,13-dibutyrate (P(Bu)2) induced binding between human lymphocytes.
The mechanisms, cell surface structures, and cell types involved in the phorbol 12,13-dibutyrate (P(Bu)2)-induced binding between human lymphocytes were studied. Induction of cell aggregation by 20 min treatment with P(Bu)2 required Ca2+, an intact membrane, functional microfilaments, and the possible participation of an esterase or, less likely, a protease. Trypsin-sensitive cell surface structures were needed and neuraminidase (NANase) treatment slightly increased the intercellular binding. Retinoic acid, an anti-tumor promoting agent, was inhibitory. Calmodulin-dependent processes, microtubules, phospholipid methylation, intracellular levels of cyclic adenosine monophosphate, and cellular secretion did not seem to be involved. Cell conjugation between 24 hr P(Bu)2-treated and untreated cells required participation of trypsin-sensitive cell surface structures in each of the interacting cells and NANase treatment of one partner slightly increased the intercellular binding. Thymocytes, T cells, mature B and Epstein-Barr virus-transformed B cells aggregated while pre-B, early B, and intermediate B lymphocytes derived from representative malignancies did not. The lack of aggregation was not due to the absence of phorbol ester receptors. It is concluded that the P(Bu2)-induced intercellular binding is mediated by cell surface proteins, depends on certain enzymatic activities and metabolic events and involves certain cell types.
D000596:Amino Acids / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002449:Cell Aggregation / Q000187:drug effects; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects*; D008565:Membrane Proteins / Q000502:physiology; D009439:Neuraminidase / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000494:pharmacology*; D010704:Phorbols / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology; D014357:Trypsin / Q000494:pharmacology
D000596:Amino Acids; D008565:Membrane Proteins; D010703:Phorbol Esters; D010704:Phorbols; D011480:Protease Inhibitors; D015240:Phorbol 12,13-Dibutyrate; D009439:Neuraminidase; D014357:Trypsin