Anti-CD11b/CD18 antibodies reduce inflammation in acute colitis in rats

Abstract

SUMMARYThe influx of monocytes and neutrophils into the inflamed tissue could be an important aspect in the pathogenesis of inflammatory bowel disease (IBD). A membrane protein involved in the monocyte/neutrophil adherence to endothelium is CDllb/CDI8 or aM,82 (complement receptor type 3 = CR3). In the present study the role of CDII b/CDI8 in experimental IBD was studied by treatment with ED7 and OX42, two MoAbs against CDllb/CDI8. Colitis was induced in rats by a single, rectal administration of 30mg 2,4,6-trinitrobenzene sulfonic acid (TNBS) dissolved in ethanol 30%. Two hours before and 3 days after induction of colitis, the animals were given an i.v. dose of O'5 mg of either ED7 or OX42 in I ml PBS. Controls received PBS or an irrelevant MoAb. Four days after the last treatment with the antibodies, the rats were killed, and macroscopic damage scores of the colon were determined. Macrophages and granulocytes were studied by immunohistochemistry and quantified by Interaktives Bild Analysen System (IBAS), and myeloperoxidase (MPO) activity in colonic tissue was measured. After treatment with ED7 and OX42 the mean damage score of the colon was reduced from 4·2 in IBD animals to 1·0 and 1,3, respectively. Smaller areas of ulcerations and a decrease in the number of ulcerations were observed compared with PBS-treated rats. Furthermore, the amount of infiltrating monocytes and leucocytes in the submucosa was enormously reduced, as well as MPO activity in the colonic tissue. These results show that treatment with MoAbs against CDllb/CDI8 reduces clinical signs of experimental IBD in rats by a partial blockade of infiltrating macrophages and granulocytes.

Amelioration of Experimental Autoimmune Myasthenia Gravis in Rats by Neonatal FcR Blockade

“…It has also been shown that anti-CR3 mAb treatments (administration of OX42) significantly reduced the inflammation of acute colitis in rats (47). In our study, CR3-expressing cells were significantly reduced in the 1G3-treated group when compared with the vehicle-treated group.…”

Regulation of dextran sodium sulfate induced colitis by leukocyte beta 2 integrins

“…[41][42][43][44] Few studies have directly examined the role of these molecules during experimental colitis with these reports documenting modification of trinitrobenzene sulfonic acid (TNBS) colitis with anti-CD18 or CD11b/ CD18 antibodies. 45,46 We report here that the b 2 integrin LFA-1 (CD11a/CD18) plays an important pathological role, whereas Mac-1 (CD11b/CD18) provides a critical regulatory role in DSS-induced experimental colitis. Several possible explanations could account for the difference in outcome regarding CD11b.…”

Formylpeptide receptor-2 contributes to colonic epithelial homeostasis, inflammation, and tumorigenesis

“…The histological hallmarks of UC are the invasion of crypt epithelium and lamina propria by polymorphonuclear neutrophils (PMNs), disruption of epithelial lining, and ulceration in the colon. PMNs are believed to play a pivotal role in mediating tissue damage in UC (41)(42)(43). In humans, PMN accumulation is also observed in rectal biopsies of active UC patients (44,45).…”