Differential Contribution of BLT1and BLT2to Leukotriene B4-Induced Human NK Cell Cytotoxicity and Migration

Abstract

Accumulating evidence indicates that leukotriene B4(LTB4) via its receptors BLT1and/or BLT2(BLTRs) could have an important role in regulating infection, tumour progression, inflammation, and autoimmune diseases. In the present study, we showed that LTB4not only augments cytotoxicity by NK cells but also induces their migration. We found that approximately 30% of fresh NK cells express BLT1, 36% express BLT2, and 15% coexpress both receptors. The use of selective BLTR antagonists indicated that BLT1was involved in both LTB4-induced migration and cytotoxicity, whereas BLT2was involved exclusively in NK cell migration, but only in response to higher concentrations of LTB4. BLT1and BLT2expression 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 LTB4. Our findings suggest that BLT1and BLT2play differential roles in LTB4-induced modulation of NK cell activity.