Receptor natural killer cells, activation

DiaZepin Nucleosides. Four naturally occurring dia2epin nucleosides, coformycin (58), 2 -deoxycoformycin (59), adechlorin or 2 -chloro-2 -deoxycoformycin (60), and adecypenol (61), have been isolated (1—4,174,175). The biosynthesis of (59) and (60) have been reported to proceed from adenosine and C-1 of D-ribose (30,176,177). They are strong inhibitors of adenosine deaminase and AMP deaminase (178). Compound (58) protects adenosine and formycin (12) from deamination by adenosine deaminase. Advanced hairy cell leukemia has shown rapid response to (59) with or without a-or P-interferon treatment (179—187). In addition, (59) affects interleukin-2 production, receptor expression on human T-ceUs, DNA repair synthesis, immunosuppression, natural killer cell activity, and cytokine production (188—194). 

Based upon recent controlled studies, there is considerable evidence that opioids such as morphine induce substantial effects on immune status. For example, it has been shown that morphine administration is associated with alterations in a number of immune parameters, such as natural-killer cell activity [12,13], proliferation of lymphocytes, [13, 14] antibody production [15,16], and the production of interferon [17]. Studies in our laboratory have shown that acute morphine treatment in rats suppresses splenic lymphocyte proliferative responses to both T- and B-cell mitogens, splenic natural-killer cell activity, blood lymphocyte mitogenic responsiveness to T-cell mitogens, and the in vitro production of the cytokines interleukin-2 and interferon-y [18-22], Furthermore, the immune alterations induced by morphine are dose-dependent and antagonized by the opioid-receptor antagonist, naltrexone (e.g., [22]). 

Another site of action for opioids is through the regulatory actions of the central nervous system (CNS) on the immune system. Substantial evidence supports the existence of a complex, bidirectional link between the CNS and the immune system (e.g., [65]). Experimental evidence indicates that morphine s immunomodulatory effects involve central opioid receptors. An initial study by Shavit and colleagues [12] found that systemic administration of morphine, but not N-methylmorphine (a form of morphine which does not readily penetrate the blood-brain barrier), produces a naltrexone-reversible suppression of splenic natural killer cell activity in the rat. That same study showed that intracerebroventricular (icv) administration of morphine dose-dependently suppresses... 

Coe, C.L. and Erickson, C., Stress decreases natural killer cell activity in the young monkey even after blockade of steroid and opiate hormone receptors, Dev. Psychobiol., 30, 1, 1997. 

Harish A, Hohana G, Fishman P, Amon O, Bar-Yehuda S (2003) A adenosine receptor agonist potentiates natural killer cell activity. Int J Oncol 23(4) 1245-1249 Hart DN (1997) Dendritic cells unique leukocyte populations which control the primary immune response. Blood 90(9) 3245-3287... 

Brown MG, Dokun AO, Heusel JW, Smith HR, Beckman DL, Blattenberger EA, Dubbelde CE, Stone LR, Scalzo A A, Yokoyama WM (2001) Vital involvement of a natural killer cell activation receptor in resistance to viral infection. Science 292 934-937... 

Lopez-Botet M, and Bellon T. (1999) Natural killer cell activation and inhibition by receptors for MHC class I. Curr Opin Immunol 11 301-307... 

Won, S.J., Chuang, Y.C., Huang, W.T., Liu, H.S. and Lin, M.T. (1995) Suppression of natural killer cell activity in mouse spleen lymphotytes hy several dopamine receptor antagonists. Experientia, 51, 343-348. 

Human selenium supplementation (e.g., 200 pg/ day), even in apparently selenium-replete individuals receiving a diet providing >120 pg Se/day, was able to stimulate the proliferation of activated T cells of the immune system. It eHcited an enhanced response to antigen stimulation, an enhanced ability to generate cytotoxic lymphocytes, an enhanced ability to destroy tumor cells, and increased natural killer cell activity. Growth-regulatory interleukin-2 receptors on the surface of activated lymphocytes and natural killer cells became upregulated. 

Moretta A, Bottino C, Vitale M, Pende D, Cantoni C, Mingari MC, Biassoni R, Moretta L Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis. Annu Rev Immunol 2001 19 197-223. 

Carson W-E, Giri JG, Lindemann MJ, Linett ML, Ahdieh M, Paxton R, Anderson D, Eisenmann J, Grabstein K, Cahgiuri MA Interleukin (ILJ-15 is a novel cytokine that activates human natural killer cells via components of the IL-2 receptor. J Exp Med 1994 180 1395-1403. 

When a cell is infected with a virus, the latter utilises the metabolic machinery within the host cell to generate viral proteins, RNA and DNA to produce more virus particles which then escape to infect other cells. The process is stopped by death of the host cells so that generation of new viruses is halted. The major mechanism that results in death of the host cell is apoptosis. The cells that are responsible for the death of the infected cells are either cytotoxic lymphocytes or natural killer cells. Death is caused either by release of toxic biochemicals and/or proteolytic enzymes or by binding to a death receptor, which is present on many cells. The entry of proteolytic enzymes or binding to the death receptor results in activation of initiator caspases. These activate effector caspases that cause damage to the cell which results in death due to apoptosis (Chapter 17 Figures 17.28, 29 and 30). 

IL-2 (Proleukin) is a cytokine that promotes the proliferation, differentiation, and recruitment of T and B lymphocytes, natural killer cells, and thymocytes. Human recombinant IL-2 is designated as rIL-2. rIL-2 binds to IL-2 receptors on responsive cells and induces proliferation and differentiation of T helper cells and T cytotoxic cells. It also can induce B-lymphocyte proliferation, activate macrophage activity, and augment the cytotoxicity of natural killer cells. 

The opioids modulate the immune system by effects on lymphocyte proliferation, antibody production, and chemotaxis. In addition, leucocytes migrate to the site of tissue injury and release opioid peptides, which in turn help counter inflammatory pain. However, natural killer cell cytolytic activity and lymphocyte proliferative responses to mitogens are usually inhibited by opioids. Although the mechanisms involved are complex, activation of central opioid receptors could... 

Nykjaer A, Petersen CM, Moller B, Andreasen PA, Gliemann J. Identification and characterization of urokinase receptors in natural killer cells and T-cell-derived lympho-kine activated killer cells. FEBS Lett 1992 300(1) 13—17. 

Interferon gamma binds to different cell surface receptors than alpha and beta Specific effect of interferon gamma include enhancement of oxidative metabolism of macrophages, antibody-dependent cellular cytotoxicity, activation of natural killer cells, and expression of Fc and major histocompatibility antigens While all alpha interferon have similar biological effects, not all activities shared by each and in many cases the extent of activity various substantially for each interferon subtype... 

Strong, R. K. (2002). Asymmetric ligand recognition by the activating natural killer cell receptor NKG2D, a symmetric homodimer. Mol. Immunol. 38, 1029-1037. 

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