Immunohistochemical Research Of CD40 Expression In Pulpitis

Pulpitis is one of the familiar oral disease following the dental cariese, which is a inflammation mainly from the Gram negtive bacterial infection. The inflammatory reaction is similar to the other parts of the body, including non-specific inflammatory reaction and specific immunity, that is marked by the neutrophils migrating out of the blood vessel and tending to the center of the inflammation in the effect of the injury factors such as bacteria and its toxic metabolite, and monocyte / macrophage phagocytizing the infectious agent, presenting the antigen to the T lymphocyte and releasing various cytokines, inducing the T lymphocyte mediate immunity reaction to eliminate the pathogen, in the meantime of the killing and eliminating the bacteria and its toxic metabolite, the organism getting damaged and destroyed.CD40 is transmembrane glycoprotein typeⅠ,belonging to the tumour necrosis factor receptor (TNF2R) superfamily. CD40L (CD154, gp39) is transmembrane glycoprotein typeⅡ,also called TRAP (TNF-related activation protein) belonging to the tumour necrosis factor (TNF) superfamily. CD40- CD40 ligand CD40L)is a rightness of protein member complementary with each other, and the couple of co-stimulatory molecules is important to specific immune response system in the body, participating in humoral and cellular immune responses.. It plays the key role in B cell activation, proliferation and differentiation, as well as the antibody producing and the same type conversion. It also plays an important modulatory role in T cell activation and responsiveness cytokine secretion. Its expression abnormality is closely related with some inflammatory reaction, the occurrence of autoimmune diseases and immunologic deficiency disease.Kinds of researches have proved that CD 40 expressed upgrade in inflammatory disease, and CD40/CD40L interactions could promote producing of many kinds pro-inflammatory cytokines and chemokines, which play important role in the genesis and development of the inflammation. Monocyte / macrophage CD40-CD40L interactions could induce the producing of pro-inflammatory cyokines and chemokines , such as IL-1αβ,IL-6,IL-8,IL-10,IL-12,TNF-αand macrophage inflammatory protein -1α(MIP-1α),which mediate and regulate the immune response and inflammatory reaction , stimulate haematogenesis function , participate in the reparation of the organism. CD40L also can induce monocyte produce PGE2. In focal inflammation , activated T cells express CD40L on the surface ,and CD40/CD40L interactions promote local endothelial cell and monocyte in tissue to produce vascular endothelial growth factor.Monocyte/macrophage promote the secretion of metalloprotease (MMPs)in the effect of CD40/CD40L interactions. The macrophage is promoted to secret nitrogen monoxidum(NO) by signal system of CD40,and it plays the role in the non-specific immunity, repressing the growth of tumor cell and pathogenic microorganism, or killing them. On the peripheral blood mononuclear cells and the endothelial cell , CD 40 binding with the ligand can immediately trigger or augment cytokines,such as expression of TNF,IL-1,GM- colony-stimulating factor (CGF), I L-6 and I L-8. TNF-, IL-la, IL-4 and INF-αpromote the expression of CD40L on the endothelial cell .The CD40L expressed by the endothelial cell plays an important role in the T cell mediated chronic inflammatory reaction. CD40/CD40L act as the stimulant signal to the related cell of plaque forming in the vasoformation, and the CD40 can enhance the expression of adhesion molecule , such as E-selectin, P-selectin, VCAM-1,ICAM-1 and VLA-4, further more the up-regulation of E-selectin and VCAM-1 mediate by the CD40L doesn't depend on the TNF-, IL-1αand IL-1β.. The main effect of CD40-CD40L interactions on the neutrophils is the activation of vessel endothelial cell, releasing adhesion molecule and selectin; inducing monocyte /macrophage to produce TNF,IL-8,and attract white cells to adhere ,and pass through the endothelial cell to aggregate in the focal inflammation to release NO and superoxide radical . Nitrogen monoxidum selectively promotes monocyte /macrophage to produce IL-1 and TNF-α,represses the synthesis of IL-6,IFN-γ,IL-2,IL-3; promotes the white cells to adhere with the endothelial cell; and represses the proliferation of T cells; elevates the activity of NK cells etc .Regulate the immunity and antibiosis ,but also lead to the damage of organism and cell . The activation of CD 40 may join in the induction of inflammatory mediator and course of bony remodeling subsequently. In addition, this may induce the producing of anti-inflammatory mediator to resist the inflammation which result in the root adsorption .From now on, there has been on related report about the expression ofCD40 in the inflammatory dental pulp and the effect of CD 40 in pulpitis at home and abroad .The expression of CD40 enhance in the inflammation ,and CD40/CD40L interactions can promote promote producing of many kinds pro-inflammatory cytokines and chemokine , when the pulp was infected by the bacteria ,the damaged cells could release massive inflammatory mediators and many cytokines, we still not clear whether the release of these inflammatory mediators is related with CD40 and whether CD 40 participate in the occurrence and development of pulpitis .This study evaluated the expression of CD40 in human pulp of normal ,acute and chronic pulpitis by immunohistochemical method, and the conclusion manifested that in healthy pulp CD40 expressed very few on plasma cell and macrophage in the individual pulp tissue , however in the tissue of acute and chronic pulpitis CD40 expressed in different extent on plasma cell and macrophage. In the inflammatory reaction, the CD40L expressed on the CD4+T cell bind with the CD40 molecule on the surface of the unsensitized B cell ,subsequently trigger the activity of NF-κB/ Rel protein , transmit the essential activation signals to B cell ,and priming the proliferation , class switch of B cell and differentiate to plasma cell which produce the immunoglobulin ,and there are IgG,IgA,IgE and IgM, the most of which is IgG in the focal inflammatory pulp tissue, so the humoral immunity is directly regulated. In addition, the CD 40 of B cell binding with CD40L of T cell is very important to cellular immunity ,more and more data shows that the CD40 binding with CD40L can quickly up-regulate the expression of T cell CD40L,and induce the producing of cytokines , in that it influence the cellular immunity . It can produce Th1 cytokine including IL-2,IFN-γand Th2 cytokine including IL-4,IL-5 and IL-10 .In irreversible pulpitis , the increase of the concentration of immunoglobulin produced by plasma cells and lymphokines released by Th cells , both of them will induce the damage of the immunopathogenesis .CD40/CD 40L signal transmission plays important role in various biologic activity of monocyte. Researches abroad deem that CD40 signal regulation of monocyte was functioned by the mRNA up-regulation of tumour necrosis factor receptor correlation factor (TRAFs)and signal pathway activation of mitogen-activated protein kinase(MAPK) , but the concrete mechanism still needs further investigation. The CD40-CD40L interaction of monocyte/ macrophage can induce producing of many kinds pro-inflammatory cytokines and chemokine,such as IL-1αβ,IL-6,IL-8,IL-10,IL-12,TNF-αand monocyte inflammatory protein-1α(MIP-1α),these cytokines mediate and regulate immune response and inflammatory reactions , stimulate haematogenesis , participate in the recovery of tissue .CD40L can also induce monocyte to produce PGE2.In focal inflammation ,activated T cells express CD40L on the surface ,and CD40/CD40L interactions promote local endothelial cell and monocyte in tissue to produce vascular endothelial growth factor(VEGF). CD40/CD40L interactions can activate producing of macrophage and fibroblast, release metalloprotease and synthesize fibrin. The membrane of activated CD4+T cell or anti-CD40-IgM antibody can induce macrophage to produce metalloprotease which is harmful for the organism ,but beneficial for the removal of the affected tissue and reconstruction.In this study, CD40 positive expression of fibroblast and vascular endothelial cell wasn't observed in the tissue of healthy pulp, acute and chronic pulpitis, which was different with previous report , the concrete reason needs further investigate .By summing up, we can assert that CD40 and the ligand CD40L interactions play important role in humoral immunity and cell mediated inflammatory reaction , and participate in course of the genesis and development of pulpitis, but the concrete effects of CD40 on the genesis and development of pulpitis and the relationship with the other cytokines need further investigation .