Mast cells have been recognized as cells playing an important role in the pathophysiology not only of allergic and immunological diseases but also of various other diseases. They participate in physiological and pathological processes through the production and release of biologically active substances such as preformed and newly generated mediators or cytokines.
The skin is one of the major target organs of IgE-mediated hypersensitivity disorders. The various mediators and/or cytokines are released from skin after mast cell activation in IgE-mediated anaphylactic reaction. The activated skin mast cells release not only histamine but also other mediators such as PGD₂ and LTB₄. These mediators contribute to pathogenesis of mast cell-related disorder such as urticaria and atopic dermatitis. In addition, it has been known that human mast cells are able to produce a variety of cytokines such as IL 4, IL-5, IL 6, TNF-α and IFN-γ. These cytokines may have an important role in skin inflammation.
It has been known that an increase in number of mast cells are observed in several skin diseases. An increase in number of mast cells at the sites of lesions may affect the pathophysiology of the diseases. The results of our studies show that keratinocytes may produce some factor which induces expression of unknown factor, different from SCF, for mast cell growth on fibroblast membrane. The mast cell growth observed in our studies may be due to a novel mechanism of mast cell proliferation and differentiation. This may be important in mast cell related skin disorders.

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Masugi nephritis of WKY rats, that is characterized with the early infiltration of CD8 positive lymphocytes and monocytes/macrophages, developed severe proliferative glomerulonephritis with crescent formation. In this model, the expression of ICAM-1 and the infiltration of LFA-1 positive cells were increased in the glomeruli. The blocking studies of CD8, ICAM-1, LFA-1 and MCP-1 in this model were effective for protection of proteinuria and glomerular injury. From these data, cell surface molecules such as adhesion molecules may play important roles in the glomerulonephritis.

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Interaction of both leukocytes and endothelial cells is important for inflammation. Its process develop in the venules of microcirculation system. Thus, we visually observed flow movement of leukocyte and platelet of Behçet disease patients using artificial microcirculation model.
Venous blood of fourteen patients of Behçet disease and fifteen healthy controls were collected into syringe containing EDTA, respectively. Blood sample were whole blood diluted 4 times with plasma and PAF (10^-6M) added to whole blood.
Blood sample flow into modified cell-flow microchannels in a singlecrystal silicon substrate and the time for 100 μl of blood sample to pass through was measured.
Deformity of leukocyte (might be rolling and adhesion) and platelet aggregation were visually observed in Behçet disease patient on TV monitor. And also, mean passage time of 100 μl sample prolonged in Behçet disease patient (147.92±25.74 sec.) compared with healty control (103.91±7.58 sec.) .
This study suggested that leukocyte and platelet were already activated in patients with Behçet disease, and activated these cells resisted to flow through the microchannels and hence interfered with the flow of other blood components.

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Effects of anti-rheumatic drugs, gold sodium thiomalate (GST), methotrexate (MTX), D-penicillamine (D-P) and bucillamine (BU), on rhIL-1β-induced nitric oxide (NO) production in rat synovial fibroblast-like cells (SFC) cultured in vitro were investigated. The SFC (passage 4) were cultured for 48hrs in Dulbecco's modified Eagle's medium containing an NO inducer, LPS or rhIL-1β. NO production by SFC was assessed by using Griess reagent. RhIL-1β but not LPS, induced a significant increase in NO production in SFC. The rhIL-1β-induced NO production was inhibited by the presence of GST in a dose dependent manner, whereas MTX (100 ng/ml) had no effect. In contrast, both D-P (10 μg/ml) and BU (3 μg/ml) significantly stimulated rhIL-1β-induced NO production in SFC. This effect of SH-containing antirheumatic drugs was completely abolished by the presence of NO inhibitors, aminoguanidine (AG : 1 mM) and cycloheximide (CH : 2 μM) . AG but not CH, added at a later stage of culture (24-48hrs) abolished rhiL 1β induced NO production, indicating that these SH-compounds stimulate NO synthase activity in SFC.
The present study suggests that SH-anti-rheumatic drugs stimulate rhIL-1β-induced NO production in SFC, and that the increase in NO may partly inhibit the bone destruction in rheumatoid arthritis.

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We developed a method for the simultaneous estimation of antigenspecific IgE and IgG antibodies in the serum of rats sensitized with DNP-As. An IgE capture ELISA employing rabbit antibodies against monoclonal DNP-specific rat IgE was applied to estimate the rat IgE antibodies to DNP-As. IgE antibodies in the serum of rats sensitized with DNP-As were first detected at day 6. The IgE antibody level increased to its highest level on day 8 during the course of sensitization with DNP-As, and was sharply decreased on days 20-25.On the other hand, the IgG antibody level increased to its highest level on day 10 during the course of sensitization with DNP-As, and decreased gradually on days 15-25. From the above-mentioned results, it is shown that the elevation of the antigen-specific IgG antibody level decreases the antigen-specific IgE antibody level in rats sensitized with DNP-As.

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The clinical efficacy of an extracorporeal granulocyte removal column (G-1) was investigated in two groups of patients with rheumatoid arthritis (RA) . Group I (n=85) received a total of 4 apheresis, one apheresis per week ; Group II (n=79) received a total of 8 apheresis, two apheresis per week. In both groups, the duration of each apheresis was 60 minutes, at a flow rate of 30 ml/minute. With respect to safety, 164 cases (patients), with respect to efficacy and usefulness, 143 cases and with respect to maintained effectiveness, 65 eases were assessed and the following results were obtained.
1) Two weeks after the last apheresis, overall improvement was 49.7% ; in Group I, 50.6% ; in Group II, 48.4%. Overall safety was 94.5% ; in Group, 96.5% ; in Group II, 92.4%. Overall usefulness was 49.7% ; in Group I, 50.6% ; in Group II, 48.4%. The results of the two groups were not significantly different.
2) At 12 weeks after the end of the treatment with G-1, the overall maintained effectiveness was 72.3% ; in Group I, 81.6% and in Group II, 59.3% ; indicating continuation of effects for 12 weeks after 4 weeks treatment. In both groups, the effectiveness of G-1 assessed at the conclusion of observations period was statisti-cally significant (p <0.05) .
3) The incidence of adverse events was very low, 3 cases with recovery without interruption of treatment, plus 3 cases of abnormal clinical laboratory tests.
4) The joint symptoms (number of joints with swelling or pain) were reduced by 50% in 67.1% of patients. There was immediate improvement, within one week after the initiation of treatment in 35.7% of patients.
5) There was improvement of anemia and plasma albumin.
The results of this clinical investigation indicate that patients with rheumatoid arthritis can benefit from the apheresis treatment with G-1 to eliminate the granulocytes in part from their peripheral blood and also to reduce joint symptoms in two third of the patients. The G-1 treatment appears to be safe, producing rapid and long lasting clinical effect.

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Urinary pyridinoline (U-Py) is a useful marker of bone and cartilage loss in rheumatoid arthritis (RA) . The serum pyridinoline (S-Py) concentration instead of U-Py was measured both in rats with adjuvant-induced (AA) and mice with collagen-induced (CIA) arthritis by high perfomance liquid chromatography (HPLC) . On the seventh day after adjuvant innoculation, the AA rats showed a significant increase in S-Py levels. The level of S-Py was gradually increased with the development of AA. Moreover, in CIA mouse, another arthritic model, on sixty days after innoculation of the type II collagen the S-Py level was also significantly higher than that in the normal mice.
These findings indicate that the measurement of S-Py instead of U-Py may be useful as marker of bone and cartilage destruction in patients with rheumatoid arthritis.

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Effects of salazosulfapyridine (SASP) and bucillamine (Bc), as disease-modifying antirheumatic drugs (DMARDs), on an active Arthus reaction and a delayed-type hypersensitivity (DTH) response were studied. SASP and Bc significantly suppressed the active Arthus reaction and DTH response. SASP and Bc also increased some cytokines in the DTH mice serum, such as interferon (IFN) -γ, interleukin (IL) -4, and IL-10.
These results suggest that SASP and Bc activate all types of T cells, especially Th0 and Th2 involved in type IV (delayed-type) hypersensitivity, and also suppress type III hypersensitivity activated with immune complex.

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