Oxidative Metabolism, Cytoskeletal System, and Calcium Entry of Leukocytes in the Phenomenon of Sensitizing Cancer Extract- induced Leukocyte Adherence Inhibition1

We examined some of the metabolic events that regulate sensitizing cancer extract-induced leukocyte adherence inhi bition and found that human leukocytes adhere in a compara tively passive manner to glass in serum-free medium. Adher ence of leukocytes to glass did not require oxidative metabo lism, 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, gen erated 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 leukotriene mediator from armed monocytes. Leu kocyte adherence inhibition requires many of the same physi ological events that chemokinesis and chemotaxis do and is thus an assay to study either immunologically released chemoattractants or chemoattractants themselves on leukocyte locomotion.