Differential Contribution of BLT(1) and BLT(2) to Leukotriene B(4)-Induced Human NK Cell Cytotoxicity and Migration

Accumulating evidence indicates that leukotriene B(4) (LTB(4)) via its receptors BLT(1) and/or BLT(2) (BLTRs) could have an important role in regulating infection, tumour progression, inflammation, and autoimmune diseases. In the present study, we showed that LTB(4) not only augments cytotoxicity by NK cells but also induces their migration. We found that approximately 30% of fresh NK cells express BLT(1), 36% express BLT(2), and 15% coexpress both receptors. The use of selective BLTR antagonists indicated that BLT(1) was involved in both LTB(4)-induced migration and cytotoxicity, whereas BLT(2) was involved exclusively in NK cell migration, but only in response to higher concentrations of LTB(4). BLT(1) and BLT(2) expression increased after activation of NK cells with IL-2 and IL-15. These changes of BLTR expression by cytokines were reflected in enhanced NK cell responses to LTB(4). Our findings suggest that BLT(1) and BLT(2) play differential roles in LTB(4)-induced modulation of NK cell activity.