Evidence in advanced cancer of an activated leukocyte state to explain the reversible defect in transmembrane signaling and leukocyte adherence inhibition to extracts of cancer.
When leukocytes bind tumor antigen, a transmembrane signal induces the cascade of physiological changes that result in leukocyte adherence inhibition (LAI). Leukocytes from patients with early stages of cancer exhibited transmembrane potential (delta psi) changes and LAI when incubated with a cancer extract of the same organ and histogenesis, whereas leukocytes from patients with advanced cancer did not. The refractoriness was reversed by transiently raising intracellular cyclic AMP. LAI is produced by leukotrienes and leukocytes from patients with advanced cancer were refractory to leukotriene-induced delta psi changes which was also restored by raising intracellular cyclic AMP. Moreover, leukocytes could be made refractory to delta psi changes: leukocytes from patients with early cancer when preincubated with a breast cancer extract showed no delta psi change with a second exposure; and leukocytes from control subjects preincubated with leukotrienes showed no delta psi change with a second exposure. The responsive population of leukocytes in LAI to either the specific cancer extract or leukotrienes consisted of about 35 to 42% of the adherent leukocytes. The responsive leukocytes in advanced cancer were already nonadherent, accounting for the 39% increased nonadherence with the control extract. Raising cyclic AMP decreased nonadherence by 39%. The results suggest that leukotrienes and other chemoattractants released in vivo by immune cells binding tumor antigen have stimulated the changes in leukocytes in advanced cancer. However, the unresponsiveness seems to be because of appropriate expression of physiological changes triggered by antigen and chemoattractant stimuli.
D001943:Breast Neoplasms / Q000097:blood*; D005260:Female; D006801:Humans; D007158:Immunologic Techniques; D007957:Leukocyte Adherence Inhibition Test; D007962:Leukocytes / Q000276:immunology / Q000503:physiopathology*; D008564:Membrane Potentials; D013189:SRS-A / Q000502:physiology
D013189:SRS-A