A Study Of The Relation Between Mast Cell And Scleroderma

Objective: Scleroderma is a kind of connective tissue disease which is local or diffuse fibrosis or sclerosis. It is involved in the skin and the connective tissue of the internal organs. Finally it is left by the atrophy of the skin. The pathogenesis of scleroderma is not understood. in recent study, it is found that autoimmune mechanisms, vascular damage and fibroblasts activation play important roles. Mast cells (MC) are tissue-dwelling cells, which are rich of cytoplasm particles and derived from the hematopoietic precursor. MC play critical roles in allergic reaction and have been associated with the physiopathology progress of other diseases, such as congenital and acquired immune response, tissue injury, fibrosis and so on. In vitro study, it is suggested that MC play important roles in increasing the proliferation of fibroblast and promoting the fiber formation. MC express and store tumor necrosis factorα(TNF-α). Once MC are activated, TNF-αmay be released immediately. TNF-αis a kind of pro-inflammatory cytokine, which is expressed by many kinds of cells and plays an important role in immunological regulation and mediating inflammatory reaction. Meanwhile, TNF-αmay stimulate more other cytokines secreted and accelerate the development of inflammatory reaction. In animal investigations, TNF-αstimulated the proliferation of the fibroblast and increased the chemiotaxis and the secretion of the matrix protein. It is found MC can also express the macrophage migration inhibiting factor (MIF) in recent studies. MIF possesses much biologic activity. MIF can inhibit the ambulation of the macrophage and elevate pellant activity of the macrophage to extraneous material. Moreover, MIF play a key role in promoting the proliferation of the fibroblast and inhibiting the apoptosis of the fibroblast. This study is designed to explore the roles of MC, TNF-αand MIF in the development of scleroderma and offer the original theoretical foundation for the treatment.Materials and Methods: The patients were derived from the dermatology department of the Fourth Affiliated Hospital of Hebei Medical University from May 2003 to Sep 2007, who were diagnosed as scleroderma clinically and histopathologically. They had no other systemic diseases or dermatosis and had no treatment in a month. These cases included 12 males and 8 females, age changed from 16 to 52 years (mean 28.12±4.84), course changed from 2 to 24 months (mean 6.23±5.12). The twenty healthy specimens which were from the skin of surgical traumatic patients were taken as controls. The controls included 14 males and 6 females; age changed from 18 to 50 years (mean 30.13±6.12) and had no other systemic diseases. There was no significant difference in sex and age between the patients and controls. HE staining was used in the histopathology. MC were measured by toluidine blue special staining (TB). The number of MC and the degranulation were analyzed by 2-independent sample compared t test. The expression of TNF-αand MIF was measured by immunohistochemisry. The results were analyzed by Mann-Whitney U rand sum test and Spearman's rank correlation test. The results were analyzed by SPSS13.0 statistic software.Results:1 Toluidine blue special stainingThe plasmic grains of MC were stained with prunosus and the nucleus stained with blue. In the lesions of scleroderma, the size of MC was different, the shape was various, the edge was unclear and the degranulation was massive. Conversely, in controls, the shape of MC was round or orbicular-ovate, boundary was orderly and slick, the particles of periplast was homogeneous, and the degranulation was minor. It was found that the number of MC in scleroderma (31.95±9.65 pie/HP) was more than that of controls (20.00±3.83 pie/HP), there was significance difference (t=3.734, p<0.01), and the proportion of the degranulation in scleroderma (80.84±5.72%) was higher than in controls (13.41±5.87%). There was significance difference (t=36.810, p<0.01).2 Immunohistochemistry2.1 TNF-αwas expressed on cell membranes and cytoplasm of full epidermis layer and vascular endothelia cell in dermis superficial layer. In the lesions of scleroderma, there were 12 cases (+++), 5 cases (++), 3 cases (+), 0 case (-); in the lesions of the controls, there were 1 case (+++), 5 cases (++), 10 cases (+), 4 cases (-). The level of TNF-αin scleroderma was higher than that in the controls. There was significance difference (Z=-4.057, p<0.01).2.2 MIF was expressed on cell membranes and cytoplasm. In the lesions of scleroderma, MIF was expressed on the full epidermis, acinar and ductal segments of the sweat glandswhich was infiltrated by mononuclear cells, as well as the endothelial cells of small dermal vessels. The level of MIF in scleroderma was higher than that in the controls. There was statistic significance difference (Z=-4.563, p<0.01).Conclusion:1 The number of MC in the lesions of scleroderma was larger, and the deregulation of MC was more massive. We speculated that MC as important effective cells perhaps might be involved in the pathogenesis of scleroderma. MC might influence directly proliferation and differentiation of the fibroblast or/and release mediators of inflammation and cytokines to promote excessive fibrosis.2 The level of TNF-αin the lesions of scleroderma was higher than that of controls. It suggested that the high level of TNF-αmight lead to damage the balance of generation and degradation of collagen and matrix and as a result of excessive fibrosis. 3 The level of MIF in the lesions of scleroderma was higher than that of controls. It suggested that MIF might expand inflammatory reaction and stimulate hyperplasia of fibroblast and collagen fibers, which led to the excessive deposition of collagen fibers.4 MIF and TNF-αwere secreted by MC. MC, MIF and TNF-αwere all involved in the pathogenesis of scleroderma. Their roles were synergetic, which led to excessive fibrosis of collagen fibers.