Oxidative metabolism, cytoskeletal system, and calcium entry of leukocytes in the phenomenon of sensitizing cancer extract-induced leukocyte adherence inhibition.
We examined some of the metabolic events that regulate sensitizing cancer extract-induced leukocyte adherence inhibition and found that human leukocytes adhere in a comparatively passive manner to glass in serum-free medium. Adherence of leukocytes to glass did not require oxidative metabolism, microtubules, microfilaments, or calcium entry, whereas leukocyte mobility excited by sensitizing cancer extract did. Calcium antagonists, lanthanum chloride, cromolyn sodium, nifedipine, trifluoperazine, and lidocaine, prevented sensitizing cancer extract-induced leukocyte mobility. Calcium agonist, ionophore A23187, excited leukocyte mobility. Ouabain, which inhibits Na+-K+-adenosine triphosphatase and may increase intracellular Ca2+ as a result, also excited leukocyte mobility. Monocytes, armed with serum from patients with early cancer and challenged with the same sensitizing tumor antigen, generated a leukotriene mediator that excited leukocyte mobility; cromolyn sodium, nifedipine, and trifluoperazine antagonized the synthesis of the mediator. The calcium antagonists inhibited the leukotriene mediator and authentic leukotrienes B4, C4, and D4 from exciting leukocyte mobility. The results showed that leukocyte mobility, excited by sensitizing cancer extract, is an active process depending upon immunologically triggered release of a leukotriené mediator from armed monocytes. Leukocyte adherence inhibition requires many of the same physiological events that chemokinesis and chemotaxis do and is thus an assay to study either immunologically released chemoattractants or chemoattractants themselves on leukocyte locomotion.
D000255:Adenosine Triphosphate / Q000097:blood; D000818:Animals; D002118:Calcium / Q000097:blood*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003599:Cytoskeleton / Q000378:metabolism*; D006168:Guinea Pigs; D006801:Humans; D007957:Leukocyte Adherence Inhibition Test; D007962:Leukocytes / Q000378:metabolism / Q000648:ultrastructure; D009000:Monocytes / Q000187:drug effects; D009369:Neoplasms / Q000032:analysis*; D010042:Ouabain / Q000494:pharmacology; D014020:Tissue Extracts / Q000494:pharmacology
D002121:Calcium Channel Blockers; D014020:Tissue Extracts; D010042:Ouabain; D000255:Adenosine Triphosphate; D002118:Calcium