Interleukin leukocyte signaling

The influence of DHA on leukocyte signaling has focused on several membrane proteins, including surface receptors, ion channels, kinases, phosphatases, and phospholipases. Here, we examine three examples germane to leukocytes tlie interleukin-2 receptor (IL2R), protein kinase C, and calcium channels (i.e., calcium mobilization). 

Interleukins comprise a group of cytokines secreted by leukocytes involved in signaling between cells of the immune system. At least 23 distinct ILs have been identified. Because IL-1 to IL-10 have been described in a previous review article (E7), only the recently discovered ILs continuing from IL-11 are described in what follows. 

In addition to cytotoxic T cells, there are helper T cells (Th cells), whose function it is to produce soluble signaling proteins called cytokines, which include the interleukins. Th cells interact with macrophages. Table 5-2 summarizes the functions of the various leukocytes of the immune system. 

Rothlein, R., Kishimoto, T. K., and Mainolfi, E. (1994) Cross-linking of ICAM-1 induces co-signaling of an oxidative burst from mononuclear leukocytes. J. Immunol. 152,2488-2495. Metinko, A. P., Kunkel, S. L., and Stricter, R. M. (1992) Anoxia-hyperoxia induces monocyte derived interleukin-8. J. Clin. Invest. 90,791-798. 

Beside activities not requiring receptor-mediated signaling, such as the activation of selected protein kinase C (PKC) isoforms (Shearman etal, 1989 Nishizuka, 1989), it is the presence of ALXR in leukocytes, synovium and other tissues that allows the expression of the potent anti-inflammatory activities of LXA (Takano et al., 1997 Sodin-Semrl et al., 2000 Chiang et al., 2000). These receptor-mediated activities include the abatement of leukocyte chemotaxis in response to LTB, peptides and other pro-inflammatory agents inhibition of the synthesis and release of many other mediators, such as the interleukins IL-6 and IL-8 and proteolytic enzymes and modulation of cell proliferation (Clish et al, 1999 Claria etal., 1996 Sodin-Semrl etal., 2000). 

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