NK CELL-MEDIATED KILLING OF AML BLASTS - ROLE OF HISTAMINE, MONOCYTESAND REACTIVE OXYGEN METABOLITES

Blasts recovered from patients with acute myelogenous leukaemia (AML) were lysed by heterologous natural killer (NK) cells treated with NK c ell-activating cytokines such as interleukin-2 (IL-2) or interferon-al pha (IFN-alpha). The cytokine-induced killing of AML blasts was inhibi ted by monocytes, recovered from peripheral blood by counterflow centr ifugal elutriation. Histamine, at concentrations exceeding 0.1 mu M, a brogated the monocyte-induced inhibition of NK cells; thereby, histami ne and IL-2 or histamine and IFN-alpha synergistically induced NK cell -mediated destruction of AML blasts The effect of histamine was comple tely blocked by the histamine H2-receptor (H2R) antagonist ranitidine but not by its chemical control AH20399AA. Catalase, a scavenger of re active oxygen metabolites (ROM), reversed the monocyte-induced inhibit ion of NK cell-mediated killing of blast cells, indicating that the in hibitory signal was mediated by products of the respiratory burst of m onocytes. It is concluded that (i) monocytes inhibit anti-leukemic pro perties of NK cells, (ii) the inhibition is conveyed by monocyte-deriv ed ROM, and (iii) histamine reverses the inhibitory signal and, thereb y, synergizes with NK cell-activating cytokines to induce killing of A ML blasts.