Dissecting the phospholipid signaling pathways triggered by Fc receptors in human immune effector cells

Abstract

Receptors for the constant region of immunoglobulins (FcRs), play a pivotal role in linking up the humoral and cellular arms of the immune system. Upon receptor aggregation, intracellular signaling cascades are triggered via the recruitment and activation of non-receptor tyrosine kinases, leading to the release of potent proinflammatory mediators, including: cytokines, metalloproteases, eicosanoids, histamine, and the oxidative burst. Thus, understanding the intracellular signaling pathways triggered by FcR has profound therapeutic potential. In my study, I have identified novel pathways triggered by FcRs, in immune-effector cells, these include: the identification of the novel calcium-independent Phospholipase A2 (iPLA2), activated by FcgR??, to be responsible for the generation of arachidonic acid and eicosanoids; and the discovery that the Phospholipase D and Sphingosine kinase pathways play important roles in the activation of the transcription factor NF-kB, production of cytokines, eicosanoids and release and activation of matrix metalloproteinases.