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. 1995 Aug;101(2):351–356. doi: 10.1111/j.1365-2249.1995.tb08363.x

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

M J Palmen 1, C D Dijkstra 1, M B van der Ende 1, A S Peña 1, E P van Rees 1
PMCID: PMC1553253  PMID: 7648720

Abstract

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Albelda S. M., Buck C. A. Integrins and other cell adhesion molecules. FASEB J. 1990 Aug;4(11):2868–2880. [PubMed] [Google Scholar]
  2. Barbé E., Damoiseaux J. G., Döpp E. A., Dijkstra C. D. Characterization and expression of the antigen present on resident rat macrophages recognized by monoclonal antibody ED2. Immunobiology. 1990 Dec;182(1):88–99. doi: 10.1016/S0171-2985(11)80586-3. [DOI] [PubMed] [Google Scholar]
  3. Binder M., Dolezal I., Wolff K., Pehamberger H. Stereologic estimation of volume-weighted mean nuclear volume as a predictor of prognosis in "thin" malignant melanoma. J Invest Dermatol. 1992 Aug;99(2):180–183. doi: 10.1111/1523-1747.ep12616803. [DOI] [PubMed] [Google Scholar]
  4. Chuluyan H. E., Issekutz A. C. VLA-4 integrin can mediate CD11/CD18-independent transendothelial migration of human monocytes. J Clin Invest. 1993 Dec;92(6):2768–2777. doi: 10.1172/JCI116895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Damoiseaux J. G., Döpp E. A., Calame W., Chao D., MacPherson G. G., Dijkstra C. D. Rat macrophage lysosomal membrane antigen recognized by monoclonal antibody ED1. Immunology. 1994 Sep;83(1):140–147. [PMC free article] [PubMed] [Google Scholar]
  6. Damoiseaux J. G., Döpp E. A., Dijkstra C. D. Cellular binding mechanism on rat macrophages for sialylated glycoconjugates, inhibited by the monoclonal antibody ED3. J Leukoc Biol. 1991 May;49(5):434–441. doi: 10.1002/jlb.49.5.434. [DOI] [PubMed] [Google Scholar]
  7. Damoiseaux J. G., Döpp E. A., Neefjes J. J., Beelen R. H., Dijkstra C. D. Heterogeneity of macrophages in the rat evidenced by variability in determinants: two new anti-rat macrophage antibodies against a heterodimer of 160 and 95 kd (CD11/CD18). J Leukoc Biol. 1989 Dec;46(6):556–564. doi: 10.1002/jlb.46.6.556. [DOI] [PubMed] [Google Scholar]
  8. Dhabhar F. S., Miller A. H., Stein M., McEwen B. S., Spencer R. L. Diurnal and acute stress-induced changes in distribution of peripheral blood leukocyte subpopulations. Brain Behav Immun. 1994 Mar;8(1):66–79. doi: 10.1006/brbi.1994.1006. [DOI] [PubMed] [Google Scholar]
  9. Dijkstra C. D., Döpp E. A., Joling P., Kraal G. The heterogeneity of mononuclear phagocytes in lymphoid organs: distinct macrophage subpopulations in the rat recognized by monoclonal antibodies ED1, ED2 and ED3. Immunology. 1985 Mar;54(3):589–599. [PMC free article] [PubMed] [Google Scholar]
  10. Graham R. C., Jr, Karnovsky M. J. The early stages of absorption of injected horseradish peroxidase in the proximal tubules of mouse kidney: ultrastructural cytochemistry by a new technique. J Histochem Cytochem. 1966 Apr;14(4):291–302. doi: 10.1177/14.4.291. [DOI] [PubMed] [Google Scholar]
  11. Huitinga I., Damoiseaux J. G., Döpp E. A., Dijkstra C. D. Treatment with anti-CR3 antibodies ED7 and ED8 suppresses experimental allergic encephalomyelitis in Lewis rats. Eur J Immunol. 1993 Mar;23(3):709–715. doi: 10.1002/eji.1830230321. [DOI] [PubMed] [Google Scholar]
  12. Krawisz J. E., Sharon P., Stenson W. F. Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity. Assessment of inflammation in rat and hamster models. Gastroenterology. 1984 Dec;87(6):1344–1350. [PubMed] [Google Scholar]
  13. Lo S. K., Van Seventer G. A., Levin S. M., Wright S. D. Two leukocyte receptors (CD11a/CD18 and CD11b/CD18) mediate transient adhesion to endothelium by binding to different ligands. J Immunol. 1989 Nov 15;143(10):3325–3329. [PubMed] [Google Scholar]
  14. Mileski W. J., Winn R. K., Vedder N. B., Pohlman T. H., Harlan J. M., Rice C. L. Inhibition of CD18-dependent neutrophil adherence reduces organ injury after hemorrhagic shock in primates. Surgery. 1990 Aug;108(2):206–212. [PubMed] [Google Scholar]
  15. Morris G. P., Beck P. L., Herridge M. S., Depew W. T., Szewczuk M. R., Wallace J. L. Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology. 1989 Mar;96(3):795–803. [PubMed] [Google Scholar]
  16. Nathan C., Srimal S., Farber C., Sanchez E., Kabbash L., Asch A., Gailit J., Wright S. D. Cytokine-induced respiratory burst of human neutrophils: dependence on extracellular matrix proteins and CD11/CD18 integrins. J Cell Biol. 1989 Sep;109(3):1341–1349. doi: 10.1083/jcb.109.3.1341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Nielsen H. V., Christensen J. P., Andersson E. C., Marker O., Thomsen A. R. Expression of type 3 complement receptor on activated CD8+ T cells facilitates homing to inflammatory sites. J Immunol. 1994 Sep 1;153(5):2021–2028. [PubMed] [Google Scholar]
  18. Palmen M. J., Dieleman L. A., van der Ende M. B., Uyterlinde A., Peña A. S., Meuwissen S. G., van Rees E. P. Non-lymphoid and lymphoid cells in acute, chronic and relapsing experimental colitis. Clin Exp Immunol. 1995 Feb;99(2):226–232. doi: 10.1111/j.1365-2249.1995.tb05537.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Robinson A. P., White T. M., Mason D. W. Macrophage heterogeneity in the rat as delineated by two monoclonal antibodies MRC OX-41 and MRC OX-42, the latter recognizing complement receptor type 3. Immunology. 1986 Feb;57(2):239–247. [PMC free article] [PubMed] [Google Scholar]
  20. Rosen H., Gordon S. Monoclonal antibody to the murine type 3 complement receptor inhibits adhesion of myelomonocytic cells in vitro and inflammatory cell recruitment in vivo. J Exp Med. 1987 Dec 1;166(6):1685–1701. doi: 10.1084/jem.166.6.1685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Rosen H. Role of CR3 in induced myelomonocytic recruitment: insights from in vivo monoclonal antibody studies in the mouse. J Leukoc Biol. 1990 Nov;48(5):465–469. doi: 10.1002/jlb.48.5.465. [DOI] [PubMed] [Google Scholar]
  22. Ross G. D., Lambris J. D. Identification of a C3bi-specific membrane complement receptor that is expressed on lymphocytes, monocytes, neutrophils, and erythrocytes. J Exp Med. 1982 Jan 1;155(1):96–110. doi: 10.1084/jem.155.1.96. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Shappell S. B., Toman C., Anderson D. C., Taylor A. A., Entman M. L., Smith C. W. Mac-1 (CD11b/CD18) mediates adherence-dependent hydrogen peroxide production by human and canine neutrophils. J Immunol. 1990 Apr 1;144(7):2702–2711. [PubMed] [Google Scholar]
  24. Wallace J. L., Arfors K. E., McKnight G. W. A monoclonal antibody against the CD18 leukocyte adhesion molecule prevents indomethacin-induced gastric damage in the rabbit. Gastroenterology. 1991 Apr;100(4):878–883. doi: 10.1016/0016-5085(91)90259-n. [DOI] [PubMed] [Google Scholar]
  25. Wallace J. L., Higa A., McKnight G. W., MacIntyre D. E. Prevention and reversal of experimental colitis by a monoclonal antibody which inhibits leukocyte adherence. Inflammation. 1992 Aug;16(4):343–354. doi: 10.1007/BF00917626. [DOI] [PubMed] [Google Scholar]
  26. Wright S. D., Rao P. E., Van Voorhis W. C., Craigmyle L. S., Iida K., Talle M. A., Westberg E. F., Goldstein G., Silverstein S. C. Identification of the C3bi receptor of human monocytes and macrophages by using monoclonal antibodies. Proc Natl Acad Sci U S A. 1983 Sep;80(18):5699–5703. doi: 10.1073/pnas.80.18.5699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. de Haan P., de Jonge A. J., Verbrugge T., Boorsma D. M. Three epitope-specific monoclonal antibodies against the hapten penicillin. Int Arch Allergy Appl Immunol. 1985;76(1):42–46. doi: 10.1159/000233659. [DOI] [PubMed] [Google Scholar]
  28. van den Berg T. K., Brevé J. J., Damoiseaux J. G., Döpp E. A., Kelm S., Crocker P. R., Dijkstra C. D., Kraal G. Sialoadhesin on macrophages: its identification as a lymphocyte adhesion molecule. J Exp Med. 1992 Sep 1;176(3):647–655. doi: 10.1084/jem.176.3.647. [DOI] [PMC free article] [PubMed] [Google Scholar]

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