Suppressive effect of non-anaphylactogenic anti-IgE antibody on the development of dextran sulfate sodium-induced colitis

Abstract

Abstract. Inflammatory bowel disease (IBD) is a spectrum of immune-mediated chronic disorders of the intestine. Patients with IBD tend to exhibit significantly elevated levels of IgE in their serum. In general, the pathogenesis of IBD exhibits inflammatory events such as immunoglobulin E (IgE)-mediated hypersensitivity. We examined the effect of the non-anaphylactogenic anti-IgE antibody, which has been known to block IgE functions, in an animal model of ulcerative colitis induced by the oral intake of dextran sulfate sodium (DSS) for seven days. The non-anaphylactogenic anti-IgE antibody was subcutaneously injected on day 0 of DSS treatment. The disease activity index (DAI) was calculated by scoring intestinal states, including body weight loss, diarrhea, and rectal bleeding, and the activities of myeloperoxidase (MPO) and chymase were measured in the colon tissue. In addition, the expression of tumor necrosis factor (TNF)-· and cyclooxygenase (COX)-2 was determined by Western blotting. Administration of the anti-IgE antibody markedly reduced the histological damage to the colon and the DAI increment exhibited by the DSS-induced colitis. The anti-IgE antibody also significantly suppressed the activities of MPO and chymase as well as the expression of TNF-· and COX-2 in the DSS-treated colon tissue. Furthermore, the elevation of IgE levels in serum was induced by DSS and reduced by anti-IgE antibody injection. Thus, these results indicate that the IgE response played an important role in the clinical signs and the expression of inflammatory mediators in a colitis model caused by DSS treatment, suggesting that the non-anaphylactogenic anti-IgE antibody may be a useful therapeutic agent for ulcerative colitis.

Oversulfated chondroitin sulfate is a contaminant in heparin associated with adverse clinical events

“…With respect to the biological ramifications of this finding, the presence of an oversulfated chondroitin sulphate within a heparin preparation could provoke increased side effects as highly sulfated polysaccharides, such as dextran sulfate, have been shown to be potent mediators of the immune response, including hypersensitivity (16,17). The structural determination of this contaminant provides a way to identify a plausible biological role, either direct or indirect, in the onset of such adverse clinical events.…”

B Cells That Produce Immunoglobulin E Mediate Colitis in BALB/c Mice

“…A critical role for IgE has also been uncovered in a dextran sulfate sodiuminduced mouse model of colitis, where blocking IgE reduced most of the clinical signs of disease. 43 Mechanistically, IgE binds to the FcR␣1 on the surface of mast cells, and second exposure to antigen results in cross-linking of bound IgE and mast cell degranulation with release of potent inflammatory mediators. 44,45 Previous studies have shown that the anti-IgE monoclonal antibody, which binds IgE at the FcR␣1 binding site, prevents IgE from binding to the receptor on mast cells.…”

Effects ofPrunus mumeSieb. et Zucc. extract and its biopolymer encapsulation on a mouse model of colitis

“…29 IgE has been implicated in the pathogenesis of IBD, as well as providing protective immunity against some gastrointestinal nematodes. 13,30 Kang et al 31 reported that anti-IgE antibodies may be useful therapeutic agents for ulcerative colitis, because they inhibit the activation of Fc RIIb. IgM has anti-inflammatory properties, and IgM auto-antibodies have been reported to protect mice against influenza virus infection.…”