Anti-CD11b/CD18 antibodies reduce inflammation in acute colitis in rats.
The 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 CD11b/CD18 or alpha M beta 2 (complement receptor type 3 = CR3). In the present study the role of CD11b/CD18 in experimental IBD was studied by treatment with ED7 and OX42, two MoAbs against CD11b/CD18. Colitis was induced in rats by a single, rectal administration of 30 mg 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 0.5 mg of either ED7 or OX42 in 1 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 CD11b/CD18 reduces clinical signs of experimental IBD in rats by a partial blockade of infiltrating macrophages and granulocytes.
Palmen
M J
MJ
Department of Cell Biology/Immunology, Faculty of Medicine, Vrije Universiteit, Amsterdam, The Netherlands.
Dijkstra
C D
CD
van der Ende
M B
MB
Peña
A S
AS
van Rees
E P
EP
D000208:Acute Disease; D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D018821:CD18 Antigens / Q000276:immunology*; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000628:therapy*; D006098:Granulocytes / Q000166:cytology / Q000276:immunology; D007167:Immunotherapy; D016177:Macrophage-1 Antigen / Q000276:immunology*; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000906:Antibodies; D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D016177:Macrophage-1 Antigen; D009195:Peroxidase