| Monocyte chemoattractant protein-1 (MCP-1) , also called monocyte chemoatactic and activating factor (MCAF), is the first cloned and identified chemoatactic factor of the CC family, the main function of which is to activate and chemoattract monocytes /macrophages.Meanwhile, MCP-1 also has chemotactic activity for lymphocytes, natural killer cells and basophils, and induces monocytes and endotheliocytes to express adhesion molecules, to get all kinds of inflammatory cells to gather together on pathological locations and to cause an intense histamine release of basophils. It has been proved by recent researches that the expression of MCP-1 affects the expression of T helper lymphocyte associated cytokines, and the absence of MCP-1 can inhibit TH2 cells mediated immune responses. It is because MCP-1 is related to the activation of many effect cells in an inflammatory reaction that function of MCP-1 in inflammatory reactions is gradually paid more attention to.In recent years, scholars from other countries have taken deep-going researches on MCP-1 from different points of view. Many researches prove that the occurrence and development of many inflammatory diseases are closely related to MCP-1, andabnormal expressions of MCP-1 can be found in many pathological conditions, including atherosis, asthma, pulmonary fibrosis, arthritis, delayed-type hypersensitivity, sepsis, and chronic bacterial infections. Atherosis is a chronic inflammation, and concentration of monocytes under the endothelium in the early stage is considered an important factor in the occurrence of atherosis. MCP-1 plays an important role in inducing monocytes in the blood to transfer to subendothelial clearance. There are obvious increases of MCP-1 expression in atheroma of both human and experimental animals. Researches in vitro indicate that expression of MCP-1 mRNA increases obviously in both abdominal macrophages of rabbits treated with ox-LDL and ox-VLDL and human vascular endothelial cells and leiomyocytes treated with ox-LDL(18). It is obvious that MCP-1 plays a particular and vital part in the promotiom of atherosis. Corrigall et al used flow cytometry to detect the expression of functional IL-2 receptors of fibroblast-like synoviocytes in rheumatic arthritis and osteoarthritis patients, and found IL-2 and IL-16 can significantly increase the generation of MCP-1, because of which the author conjectured that MCP-1 causes the concentration of macrophages and everlasting inflammation in joints of rheumatic arthritis patients. Also, there is a large number of MCP-1 expression in gingivitis caused by bacteria. Three facts further prove the significance of MCP-1 togingivitis: First, most mononuclear phagocytes in gingivitis sites secrete MCP-1; Second, the expression of MCP-1 is closely related to the degree of inflammation; Third, MCP-1 is the main monocyte chemoatactic factor in gingival crevicular fluid. Luhan Ding et al also observed that excessive expression of MCP-1 in human renal tissues of glomerulonephritis is positively related to the expression of monocytes /macrophages, which indicates that MCP-1 may play an important part in the infiltration of monocytes in glomerulonephritis patients. These searches all indicate that MCP-1 can chemoattract monocytes and T lymphotes in vivo and induce many kinds of inflammatory diseases, and at the same time indicate that the expression and regulation of MCP-1 can benefit the treatment of inflammatory diseases. But it is rarely reported how MCP-1 is expressed in inflammatory dental pulp and how it functions in pulpitis. This article analyzes possible functions of MCP-1 in inflammatory process through researches of MCP-1 expression in dental pulp.This research used immunohistochemical methods to report positive expressions of MCP-1 to different degrees in inflammatory tissues. The main cells to express MCP-1 are monocytes /macrophages, vascular endotheliocytes and neutrophils. Inflammatory cells concentrate, infiltrate and phagocytize pathogens on lesion locations when stimulated by pathogenicmicroorganisms, inflammation occurs in pulp tissues, and in this process organic immune system participates in defensive reactions of pulp tissues against foreign injurants.Cytokine network system is activated through interactions of immunocytes and inflammatory mediators in tissues, etc, and many kinds of cytokines are released ( including IL-1, TNF-a, IL-8, MCP-1, etc ) to regulate the occurrence and development of the inflammation, resulting inevitably in tissue damage and destruction meanwhile. The expression of MCP-1 in inflammatory pulp further proves that as a inductively expressed chemoattractant, when stimulated and induced by endotoxin, bacteria releasing enzymes, metabolites, inflammatory mediators and other injurants in gingivitis, it is up-regulated in expression to participate in pulp inflammatory process. In experiments we observed expression of MCP-1 on macrophages and vascular endotheliocytes, which is similar to former reports, and which indicates that MCP-1 plays an important part in chemoattracting monocytes /macrophages and helping monocytes pass through vascular endotheliocytes to inflammatory sites. But we observed positive expression of MCP-1 on a great many neutrophils, which is different from most reports, while is similar to report of JohnstonB et al. It is speculated that the reason of MCP-1 expression of on neutrophils is that chemoattractant receptors are regulated by the action ofinflammatory cytokines, physiological significance of which is to benefit rapid entry of a large number of leukocytes to inflammatory sites, and specific mechanism of which has to be studied further.To sum up, MCP-1 expression in inflammatory pulp explains the mechanism of a significant increase of macrophages in pulpitis, and provides a new idea for treatment of pulpitis. It can be predicted that a further study of MCP-1 will help exploit a new field of pulpitis treatment, and will provide the clinic with new targets. At present, there are more and more treatment methods targeted at MCP-1 in the treatment of various inflammatory diseases, including aspects of inhibiting MCP-1 expression, of antagonists of MCP-1, of antagonists of CCR2, and of DNA vaccines, etc. A new anti-rheumatic agent, KE-298 can decrease MCP-1 expression in rat sinovium of rheumatic arthritis(19). The mutant (7ND) of second to eighth amino acid deletion on the MCP-1N end is an effective MCP-1 antagonist. The mechanism is, that in normal conditions, MCP in the form of dimmer provides two N ends to combine with MCP-1 receptors. Although the 7ND mutant /MCP-1 heterodimer can bind with receptors, they have no biological activity because of deletion of one N end(20). Plasmids with 7ND mutants injected to skeletal muscle of rats with atherosis can block inflammatory and proliferating reactions in the early stage of atherosis, and prevent further incrassation of coronary... |
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