Mjhj. Palmen et al., ANTI-CD11B CD18 ANTIBODIES REDUCE INFLAMMATION IN ACUTE COLITIS IN RATS/, Clinical and experimental immunology, 101(2), 1995, pp. 351-356
The influx of monocytes and neutrophils into the inflamed tissue could
be an important aspect in the pathogenesis of inflammatory bowel dise
ase (IBD). A membrane protein involved in the monocyte/neutrophil adhe
rence to endothelium is CD1b/CD18 or alpha M beta(2) (complement recep
tor type 3 = CR3). In the present study the role of CD 11b/CD18 in exp
erimental IBD was studied by treatment with ED7 and OX42, two MoAbs ag
ainst CD11b/CD18. Colitis was induced in rats by a single, rectal admi
nistration of 30 mg 2,4,6-trinitrobenzene sulfonic acid (TNBS) dissolv
ed in ethanol 30%. Two hours before and 3 days after induction of coli
tis, the animals were given an i.v. dose of 0.5 mg of either ED7 or OX
42 in 1 ml PBS. Controls received PBS or an irrelevant MoAb. Four days
after the last treatment with the antibodies, the rats were killed, a
nd 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 (MPG)
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 a
nimals to 1.0 and 1.3, respectively. Smaller areas of ulcerations and
a decrease in the number of ulcerations were observed compared with PB
S-treated rats. Furthermore, the amount of infiltrating monocytes and
leucocytes in the submucosa was enormously reduced, as well as MPO act
ivity in the colonic tissue. These results show that treatment with Mo
Abs against CD11b/CD18 reduces clinical signs of experimental IBD in r
ats by a partial blockade of infiltrating macrophages and granulocytes
.