Chronic alcohol consumption compromises NK cell release from the bone marrow and impairs NK cell maturation in the spleen (132.32)

Abstract

Abstract NK cells primarily originate in the bone marrow (BM). The release of these cells from BM to peripheral organs is associated with the sphingosine 1-phosphate (S1P) and S1P receptor 5 (S1PR5) signaling system. T-bet controls the expression of S1PR5 on NK cells. Chronic alcohol consumption inhibits splenic NK cell cytolytic activity and compromises NK cell release from the BM. The underlying mechanism is still unknown. Herein, we used a murine model to study the effects of chronic alcohol consumption on NK cell development in BM and spleen. Alcohol consumption increased NK cells in the BM. The increased cells were CD27hiMac-1hi. The expression of S1P5 and T-bet in splenic and BM NK cells did not change in the alcohol consuming mice. The number of NK cells in the spleen was significantly decreased. The decreased NK cells were CD27loMac-1hi. The percentage and numbers of the activating receptor, Ly49D and Ly49H, positive NK cells decreased significantly. However, the decrease in the percentage and number of the inhibitory receptor, Ly49G, Ly49C, and Ly49A, expressing NK cells was lower than the activating receptor positive NK cells. These results indicate that chronic alcohol consumption blocks NK cell release from BM at the CD27hiMac-1hi stage. The block is independent of T-bet and S1PR5 expression. The results also indicate that alcohol consumption inhibits terminal maturation of NK cells before they acquire activating Ly49 receptors in the spleen.