Lymphocyte aggregation in response to adrenergic stimulation.
A nonanemic chronic lymphocytic leukemia patient with nearly 500,000 lymphocytes/microL underwent leukapheresis when she presented with CNS symptoms and retinal vascular engorgement. Respiratory distress developed during the cell separator run, which led us to ask whether the procedure could have changed the adhesive properties of her cells. C5a desarginine, N-f-Met-Leu-Phe, adenosine diphosphate, and collagen all failed to aggregate her lymphocytes in vitro, but arachidonic acid, excess free calcium, and 4 mumol/L epinephrine did aggregate the cells. Arachidonate-induced aggregation appeared to be a toxic phenomenon: the ED50 for aggregation was statistically indistinguishable from that for cytotoxicity, and aspirin only mildly blunted the response. In contrast, epinephrine-induced aggregation was not associated with lactic dehydrogenase release or the loss of trypan blue exclusion and was blunted by propranolol; radiopindolol-binding studies confirmed the presence of a beta-adrenergic receptor. There were approximately 3,000 receptors/cell, with no statistically significant difference between normal and chronic lymphocytic leukemia B cells or between B cells and T cells (separated by rosetting techniques). The Kd for the B cells' receptor, however, was less than that for T cells by a factor of ten (P less than .01). We conclude that B cells may aggregate when stimulated and that they--like T cells--have beta-adrenergic receptors. Adrenergically mediated changes in B cell adhesiveness may play a role in regulating lymphocyte traffic; in the rare patient with truly enormous B cell counts, we postulate that they may be an occasional cause of morbidity.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002449:Cell Aggregation / Q000187:drug effects*; D002951:Citrates / Q000494:pharmacology; D019343:Citric Acid; D004417:Dyspnea / Q000209:etiology; D005260:Female; D006801:Humans; D007937:Leukapheresis / Q000009:adverse effects; D007945:Leukemia, Lymphoid / Q000473:pathology*; D008214:Lymphocytes / Q000187:drug effects* / Q000473:pathology; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D001095:Arachidonic Acids; D002951:Citrates; D011943:Receptors, Adrenergic, beta; D016718:Arachidonic Acid; D019343:Citric Acid; D000001:Calcimycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D000244:Adenosine Diphosphate; D001241:Aspirin