Modulation of natural killer cell function by alpha-adrenoreceptor-coupled signalling.

OBJECTIVE: Our previous work has shown that α-adrenoreceptor (α-AR)-coupled signaling modulates T lymphocyte function. Here, we investigate the expression of α₁- and α₂-ARs in natural killer (NK) cells and roles of the two subtypes of α-ARs and their coupled signals in modulation of NK cell function.

METHODS: NK cells were purified by Ficoll-Isopaque one-step gradient centrifugation and in discontinuous Percoll density gradients from splenic cells of rats. The mRNA expressions of α₁-ARs and α₂-ARs in NK cells were measured by reverse transcription-polymerase chain reaction (RT-PCR). Flow cytometry was employed to detect the cytotoxicity of NK cells.

RESULTS: NK cells expressed both α₁-AR and α₂-AR mRNAs. Phenylephrine, a selective α₁-AR agonist, increased the cytotoxicity of NK cells. This effect of phenylephrine was reduced by corynanthine, a selective α₁-AR antagonist, and was blocked by PLC inhibitor U-73122, but not by PKA inhibitor H-89. Clonidine, a selective α₂-AR agonist, also enhanced the cytotoxicity of NK cells. This action of clonidine was blocked by α₂-AR antagonist yohimbine or by PKA inhibitor H-89, but not by PLC inhibitor U-73122.

CONCLUSIONS: NK cells express α₁- and α₂-ARs. Activation of the either subtype of α-ARs augments NK cell function. This action of α₁-ARs is transduced by PLC, while α₂-AR effect is mediated by PKA signaling.