G protein-coupled receptors in natural killer cells

Natural killer (NK) cells are capable of killing tumor as well as virally infected cells. How these cells migrate toward the infected sites in the body is not completely understood. Chemokine receptors that belong to the heptahelical family of receptors and characteristic ally bind heterotrimeric G proteins are present in most NK cells. Recent results showed that resting NK cells highly express constitutive chemokine receptors (CCR4, CCR7, CXCR4, and CX(3)CR1) with low expression of a limited repertoire of inflammatory chemokine receptors (CCR1 and CXCR3). However, only a subset of these cells expressing the CD56(dim) and adhesion molecule(high) phenotype is capable of in vivo binding to vascular endothelium. Under pathological conditions where inflammatory cytokines are present, these cells are induced to express inflammatory chemokine receptors. Resting as well as activated NK cells also express receptors for another member of the heptahelical family of receptors that bind phosphorylated or glycosylated lysolipids. These include sphingosine I-phosphate (S1P)(1), S1P(4), and S1P(5), the receptors for S1P; lysophosphatidic acid (LPA)(1), LPA(2), and LPA(3), the receptors for LPA; and T cell death-associated gene 8, the receptor for psychosine. Similar to chemokines, S I P, LPA, and psychosine induce the chemotaxis of NK cells through heterotrimeric G proteins. However, in contrast to chemokines, which enhance the cytotoxicity of NK cells, lysolipids inhibit this function. We hope that gaining knowledge regarding the distribution of activated NK cells toward the sites of tumor growth or virally infected sites will give an advantage in designing strategies using these cells as tools for the prevention and treatment of immunodeficiencies.