A CELL-TO-CELL MEDIATED INTERACTION INVOLVING MONOCYTES AND NON-T/CD16+ NATURAL-KILLER (NK) CELLS IS REQUIRED FOR HISTAMINE H2-RECEPTOR-MEDIATED NK-CELL ACTIVATION

Histamine (10‐1 to 10‐7 M) augmcnled natural killer cell cytotoxicity(NKCC)of human CD16+, non‐Tlymphocytes in vitro against the NK‐sensitive target cells K562erythroleukaemic, Molt‐4 lymphoma, Chang liver cells and against Epstein—Barr virus (EBV)‐transformed, NK‐insensitive Daudi B‐lymphohlastoid target ceils by a mechanism of action involving a prostaglandin‐ and interleukin 1 (IL‐l)‐independent accessory function of monoeyles. No evidence for the production of intermediary. NK‐enhancing cytokines by hisiamine was obtained, indicating a cell‐to‐cell mediated interaction between monoeytes and NK cells as a plausible mechanism of action for the NK‐augmenting effeci. Monocytes recovered by countercurrent centrifugal elutriation (CCE), but not monocyles recovered by adherence, reconstituted the effect of histamine when added to non‐adherent NK cells. The development of NKCC in response to histamine was time‐dependent with (i) an induction phase, dependent on the presence of accessory monocytes and ongoing hislamine H2‐receptor activation (hulf‐maximal response required approximately 30 min treatment of large granular lymphocyte (LGL)‐enriched lymphocytes and monoeytes with histamine), and (ii) an effector phase, independent of the presence of monocytes or hislamine receptor activation. Hislamine‐activated mononuclear cells (MNC) continued to exert augmented cytotoxicity for at least 8 h after removal of histamine and monocytes. In several experiments, histamine‐activated NK‐effector cells killed > 90% of the target cells at low baseline NKCC. We suggest that histatamine may have a role in non‐specific tumour defence by regulating an earlier unrecognized interplay between monocytes and NK cells. Copyright © 1990, Wiley Blackwell. All rights reserved