The Complex Immune response in COVID-19 May be Tied to Factors Released from Activated Innate Immune Cells

“Antioxidants, such as 3-amino-L-tyrosine, protect cells from the oxidatively induced death process. Concomitant with this increase in cell death and release of protective factor (altruistic factor to protect bystander cells from death signal) is an increase in spontaneous nitric oxide production by …cells. Although NO (nitric oxide) has been seen as an immunosuppressive agent based on inhibition of mitogen-driven lymphocyte proliferation, it may activate lymphocyte differentiation and lymphokine production. Evidence for the latter conclusion is found in the fact that TNF-alpha production goes up (pro-inflammatory cytokine that can cause cell death and shock) when human peripheral mononuclear cells are activated with NO. This effect could have been the result of gamma-interferon production. Further evidence for NO immune stimulation is found in the fact that expression of IL-2 (cytokine needed for specific immune response of T cells) in CD4 + T lymphocytes increases with NF-kappa-B expression (a gene expression inducer), which follows NO stimulation. Human peripheral blood mononuclear cells, monocytes and lymphocytes, have been shown to be activated by NO, as revealed by increased NF-kappa-B-DNA binding activity, enhanced rate of glucose transport, enhanced membrane-associated tyrosine phosphatase activity, and this activation, in turn, activated src family protein kinase p56lck activity in these cells (protecting against self-programmed cell death leading to proliferation and activation of functions)….The NO induces membrane component clustering similar to that induced by antigen binding to lymphocyte cell membranes and actin polymerization induced by hydrogen peroxide and hemin. The resolution of these paradoxical effects of NO may be based not only on concentrations but also on feedback mechanisms (which could prevent serious collateral damage or, if fails, permanent damage or even death).—Type-B Cytochromes: Sensors and Switches by J.L. Kiel
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