Requirement for autologous cancer extracts and lipoxygenation of arachidonic acid for human T-cell responses in leukocyte adherence inhibition and transmembrane potential change assays.
Assays of leukocyte adherence inhibition (LAI) and transmembrane potential (delta psi) change were used to examine the responses of T-cells from control subjects and breast cancer patients when incubated with extracts of breast cancer and other tissues. Of T-cells from 25 patients with breast cancer, 21 exhibited delta psi changes or inhibition of adherence to glass when they were incubated with extracts of autologous but not allogeneic breast cancer; extracts of autologous normal breast tissue did not induce delta psi changes or LAI in T-cells from patients with breast cancer. Supernatants were collected after incubating 1 X 10(7) T-cells from patients with breast cancer or from control subjects with extracts of the autologous cancer. When the supernatants were added to either peripheral blood leukocytes or mononuclear cells from normal donors, neither delta psi changes nor LAI were detected. To still determine whether the nonadherence was mediated by chemoattractant lymphokines, the effect of inhibiting T-cell arachidonic acid metabolism was examined. The lipoxygenase pathway antagonist, 5,8,11,14-eicosatetraynoic acid, or a leukotriene antagonist, FPL 55712, inhibited T-cell LAI, but a cyclooxygenase pathway antagonist, indomethacin, did not. Moreover, authentic leukotriene B4 induced delta psi changes and LAI in T-cells. The results indicated that T-cells from patients with breast cancer recognized and bound a tumor-specific antigen in the autologous neoplastic breast tissue that transduced a transmembrane signal to trigger a series of biochemical changes, releasing lipoxygenase products of arachidonate. The lipoxygenase products, which may be important in the inflammatory response to cancer, induced a loss of T-cell adherence to glass.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001943:Breast Neoplasms / Q000276:immunology / Q000503:physiopathology*; D002448:Cell Adhesion; D005260:Female; D006801:Humans; D007700:Kinetics; D007957:Leukocyte Adherence Inhibition Test; D007962:Leukocytes / Q000276:immunology*; D008113:Liver Neoplasms / Q000276:immunology / Q000503:physiopathology / Q000556:secondary*; D008564:Membrane Potentials; D013189:SRS-A / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*
D001095:Arachidonic Acids; D013189:SRS-A; D016718:Arachidonic Acid