NK cell‐mediated killing of AML blasts: role of histamine, monocytes and reactive oxygen metabolites
2009
: Blasts recovered from patients with
acute myelogenous leukaemia(AML) were lysed by heterologous natural killer (NK) cells treated with NK cell-activating cytokines such as interleukin-2 (IL-2) or interferon-α (IFN-α). The cytokine-induced killing of AML blasts was inhibited by
monocytes, recovered from peripheral blood by
counterflow centrifugal elutriation.
Histamine, at concentrations exceeding 0.1 μM, abrogated the
monocyte-induced inhibition of NK cells; thereby,
histamineand IL-2 or
histamineand IFN-α synergistically induced NK cell-mediated destruction of AML blasts. The effect of
histaminewas completely blocked by the
histamine H2-receptor(H2R) antagonist
ranitidinebut not by its chemical control AH20399AA. Catalase, a scavenger of reactive oxygen metabolites (ROM), reversed the
monocyte-induced inhibition of NK cell-mediated killing of blast cells, indicating that the inhibitory signal was mediated by products of the
respiratory burstof
monocytes. It is concluded that (i)
monocytesinhibit anti-leukemic properties of NK cells, (ii) the inhibition is conveyed by
monocyte-derived ROM, and (iii)
histaminereverses the inhibitory signal and, thereby, synergizes with NK cell-activating cytokines to induce killing of AML blasts.
Keywords:
-
Correction
-
Source
-
Cite
-
Save
17
References
60
Citations
NaN
KQI