AFP Inhibits Naturally Immunized Siglec-5 Pathways

Chronic hepatic diseases are most important diseases that affect human’s health. Frequency of hepatic diseases have been promoted, due to global obesity, increased consumption of alcohol and increased infection of hepatitis virus. Particularly, chronic liver diseases often develop into cirrhosis. The low immunity capacity and apt to infection result in a 50% hospitalization rate of the patients with chronic hepatic diseases. Among of them,15-35% would have nosocomial infections and a higher mortality.In the natural immune system, the dysfunction of peripheral blood neutral granulocytes and monocytes in liver cirrhosis patients may be associated with bacterial infection, but the underlying mechanism is still unknown. In this study, the interplay between AFP and innate immunity dsy function is studied.AFP is a main serum protein in fetus body, mainly synthesized in liver and viteline sac then transported to other kind of tissues and cells. AFP has a various effects on innate immunity, it can inhibit natural killer cell activity, repress T cell proliferation and mitosis,reduce macrophage phagocytic function and so on. According to previous research, some autoimmune disease such as rheumatoid arthritis, multiple sclerosis and other autoimmune diseases can be buffered during pregnancy, which is most distinct at late stage of pregnancy. This correlates with an increased level of AFP. However, the link between AFP and innate immunity is still unclear.Natural immunity is also named innate or nonspecific immunity, which can be obtained through genetic. Innate immunity is a mechanism which is formed during the long-term phylogenetic and evolution as specific immunity. Innate immunity is consists of immune organ, immune cell and immune molecular, including tissue barrier(skin and mucous membrane,blood brain barrier), innate immune cells(dendritic cells,macrophages)and natural immune molecules(chemokine, interferon.etc). Some factors can affect innate immunity includes defensins, complement, lysozyme, inflammatory mediators and Siglecs (Sialic acid binding immunoglobulin).Among them, Siglecs is involved in signaling transduction and regulating function of innate immunity.Siglecs are thought to be important in regulating cell membrane receptor activation and inflammatory reaction. Siglecs-5 is one of immunomodulatory factors, it also belongs to the immunoglobulin superfamily, whose members can transduction mediated immune regulation signal through specific recognition and binding sialic acid carbohydrate side chains on glycoproteins and glycolipids. pathogenic microorganisms induce host immune response by a combination of its sialic acid surface structure with Siglecs of immune cell surface. AFP functions not only as ligands to bind with AFP receptor to regulate cell development, but also in regulating gene transcription through controlling interaction between some transcription factor and key proteins. In this study, the effect of AFP on Siglec-5 pathway activation is studied in U937 cells.Methods:(1).study of AFP binding to U937 cells or human peripheral blood neutrophils: isolated peripheral neutrophil leucocytes from healthy subjects or cultured U937 cells are used in radioreceptor assay with 1251-AFP.(2).Effects of AFP on leukocyte phagocytic of Streptococcus:prepared Streptococcus and AFP treated blood cells are used in phagocytosis assay.(3).Effects of AFP on whole blood respiratory burst capability:whole blood cells are treated with AFP first and then treated with fMLP, the burst capacity is analyzed with luminal fluorescent assay.(4).Effects of AFP on Siglec-5 expression:U937 cells are treated with AFP, then the expression of Siglec-5 is determined by flow cytometry.(5).Study of the recruitment of SHP-1/SHP-2 in Siglec-5 activation:U937 cells are treated with AFP and group B streptococcus, co-immuno precipitation method is employed to study the recruitment of Siglec-5 and SHP-l/SHP-2 following Siglec-5 activation.Results:(1).AFP can bind to U937 cells and human peripheral blood neutrophils.(2).AFP has an inhibitory effects on leukocyte phagocytosis of swine streptococcus.(3).AFP can promote ability of leukocyte respiratory burst.(4). AFP promotes expression of Siglec-5 in U937 cells.(5).activation of Siglec-5 by AFP in U937 cells induces the recruitment of SHP-1/SHP-2.Conclusions:AFP can suppress neutrophil phagocytic killing of group B streptococci by activating Siglec-5 expression. Hepatoma and high level of AFP of chronic liver disease might cause a down-regulated immunity ability and infection.