Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1994 Mar;111(3):811–818. doi: 10.1111/j.1476-5381.1994.tb14810.x

Role of CD18 in the accumulation of eosinophils and neutrophils and local oedema formation in inflammatory reactions in guinea-pig skin.

M M Teixeira 1, S Reynia 1, M Robinson 1, A Shock 1, T J Williams 1, F M Williams 1, A G Rossi 1, P G Hellewell 1
PMCID: PMC1910091  PMID: 7912627

Abstract

1. Intradermal injection of the complement fragment C5a des Arg induces local oedema formation that, in rabbits and man, is dependent on circulating neutrophils. Monoclonal antibodies to the leukocyte adhesion molecule CD11/CD18 block neutrophil accumulation and prevent neutrophil-dependent oedema formation. The role of CD11/CD18 in mediating eosinophil accumulation in vivo is less established. In this study we have used an anti-human CD18 monoclonal antibody, 6.5E, to investigate the neutrophil-dependency of oedema formation induced by C5a des Arg in guinea-pig skin. We also studied the role of CD18 in mediating eosinophil accumulation in the same model. 2. Stimulated adhesion of 111In-labelled guinea-pig neutrophils and eosinophils to serum-coated plastic was inhibited in a dose-dependent manner by 6.5E suggesting that the monoclonal antibody recognizes and blocks the guinea-pig CD18 adhesion molecule. 3. The accumulation of 111In-labelled neutrophils induced by zymosan-activated plasma (ZAP, as a source of C5a des Arg) in skin sites was reduced by up to 89% in animals treated intravenously with F(ab')2 fragments of 6.5E. ZAP-induced accumulation of 111In-labelled eosinophils was also greatly reduced (by up to 78%) by treatment with 6.5E. 4. Despite the inhibition of ZAP-induced neutrophil accumulation by 6.5E, local oedema formation in the same skin sites was unaffected, except at the top dose of ZAP, by treatment with the anti-CD18 monoclonal antibody, suggesting that the oedema response was largely neutrophil-independent. Indeed, ZAP-induced oedema formation was reduced by up to 81% by the H1 receptor antagonist, mepyramine.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
811

Selected References

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

  1. Anderson D. C., Schmalsteig F. C., Finegold M. J., Hughes B. J., Rothlein R., Miller L. J., Kohl S., Tosi M. F., Jacobs R. L., Waldrop T. C. The severe and moderate phenotypes of heritable Mac-1, LFA-1 deficiency: their quantitative definition and relation to leukocyte dysfunction and clinical features. J Infect Dis. 1985 Oct;152(4):668–689. doi: 10.1093/infdis/152.4.668. [DOI] [PubMed] [Google Scholar]
  2. Andrew D., Shock A., Ball E., Ortlepp S., Bell J., Robinson M. KIM185, a monoclonal antibody to CD18 which induces a change in the conformation of CD18 and promotes both LFA-1- and CR3-dependent adhesion. Eur J Immunol. 1993 Sep;23(9):2217–2222. doi: 10.1002/eji.1830230925. [DOI] [PubMed] [Google Scholar]
  3. Arfors K. E., Lundberg C., Lindbom L., Lundberg K., Beatty P. G., Harlan J. M. A monoclonal antibody to the membrane glycoprotein complex CD18 inhibits polymorphonuclear leukocyte accumulation and plasma leakage in vivo. Blood. 1987 Jan;69(1):338–340. [PubMed] [Google Scholar]
  4. Björk J., Hugli T. E., Smedegård G. Microvascular effects of anaphylatoxins C3a and C5a. J Immunol. 1985 Feb;134(2):1115–1119. [PubMed] [Google Scholar]
  5. Bochner B. S., Luscinskas F. W., Gimbrone M. A., Jr, Newman W., Sterbinsky S. A., Derse-Anthony C. P., Klunk D., Schleimer R. P. Adhesion of human basophils, eosinophils, and neutrophils to interleukin 1-activated human vascular endothelial cells: contributions of endothelial cell adhesion molecules. J Exp Med. 1991 Jun 1;173(6):1553–1557. doi: 10.1084/jem.173.6.1553. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bowen T. J., Ochs H. D., Altman L. C., Price T. H., Van Epps D. E., Brautigan D. L., Rosin R. E., Perkins W. D., Babior B. M., Klebanoff S. J. Severe recurrent bacterial infections associated with defective adherence and chemotaxis in two patients with neutrophils deficient in a cell-associated glycoprotein. J Pediatr. 1982 Dec;101(6):932–940. doi: 10.1016/s0022-3476(82)80013-9. [DOI] [PubMed] [Google Scholar]
  7. Cochrane C. G., Müller-Eberhard H. J. The derivation of two distinct anaphylatoxin activities from the third and fifth components of human complement. J Exp Med. 1968 Feb 1;127(2):371–386. doi: 10.1084/jem.127.2.371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Collins P. D., Weg V. B., Faccioli L. H., Watson M. L., Moqbel R., Williams T. J. Eosinophil accumulation induced by human interleukin-8 in the guinea-pig in vivo. Immunology. 1993 Jun;79(2):312–318. [PMC free article] [PubMed] [Google Scholar]
  9. DAVIES G. E., LOWE J. S. A permeability factor released from guinea-pig serum by antigen-antibody precipitates. Br J Exp Pathol. 1960 Aug;41:335–344. [PMC free article] [PubMed] [Google Scholar]
  10. Dias Da Silva W., Lepow I. H. Complement as a mediator of inflammation. II. Biological properties of anaphylatoxin prepared with purified components of human complement. J Exp Med. 1967 May 1;125(5):921–946. doi: 10.1084/jem.125.5.921. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dobrina A., Menegazzi R., Carlos T. M., Nardon E., Cramer R., Zacchi T., Harlan J. M., Patriarca P. Mechanisms of eosinophil adherence to cultured vascular endothelial cells. Eosinophils bind to the cytokine-induced ligand vascular cell adhesion molecule-1 via the very late activation antigen-4 integrin receptor. J Clin Invest. 1991 Jul;88(1):20–26. doi: 10.1172/JCI115278. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Doerschuk C. M., Winn R. K., Coxson H. O., Harlan J. M. CD18-dependent and -independent mechanisms of neutrophil emigration in the pulmonary and systemic microcirculation of rabbits. J Immunol. 1990 Mar 15;144(6):2327–2333. [PubMed] [Google Scholar]
  13. Faccioli L. H., Nourshargh S., Moqbel R., Williams F. M., Sehmi R., Kay A. B., Williams T. J. The accumulation of 111In-eosinophils induced by inflammatory mediators, in vivo. Immunology. 1991 Jun;73(2):222–227. [PMC free article] [PubMed] [Google Scholar]
  14. Fernandez H. N., Henson P. M., Otani A., Hugli T. E. Chemotactic response to human C3a and C5a anaphylatoxins. I. Evaluation of C3a and C5a leukotaxis in vitro and under stimulated in vivo conditions. J Immunol. 1978 Jan;120(1):109–115. [PubMed] [Google Scholar]
  15. Furie M. B., Tancinco M. C., Smith C. W. Monoclonal antibodies to leukocyte integrins CD11a/CD18 and CD11b/CD18 or intercellular adhesion molecule-1 inhibit chemoattractant-stimulated neutrophil transendothelial migration in vitro. Blood. 1991 Oct 15;78(8):2089–2097. [PubMed] [Google Scholar]
  16. Galea-Lauri J., Blackford J., Wilkinson J. M. The expression of CD11/CD18 molecules on rabbit leucocytes: identification of monoclonal antibodies to CD18 and their effect on cellular adhesion processes. Mol Immunol. 1993 Apr;30(6):529–537. doi: 10.1016/0161-5890(93)90027-9. [DOI] [PubMed] [Google Scholar]
  17. Harlan J. M., Killen P. D., Senecal F. M., Schwartz B. R., Yee E. K., Taylor R. F., Beatty P. G., Price T. H., Ochs H. D. The role of neutrophil membrane glycoprotein GP-150 in neutrophil adherence to endothelium in vitro. Blood. 1985 Jul;66(1):167–178. [PubMed] [Google Scholar]
  18. Hawkins H. K., Heffelfinger S. C., Anderson D. C. Leukocyte adhesion deficiency: clinical and postmortem observations. Pediatr Pathol. 1992 Jan-Feb;12(1):119–130. doi: 10.3109/15513819209023288. [DOI] [PubMed] [Google Scholar]
  19. Issekutz A. C. Vascular responses during acute neutrophilic inflammation. Their relationship to in vivo neutrophil emigration. Lab Invest. 1981 Nov;45(5):435–441. [PubMed] [Google Scholar]
  20. José P. J., Forrest M. J., Williams T. J. Human C5a des Arg increases vascular permeability. J Immunol. 1981 Dec;127(6):2376–2380. [PubMed] [Google Scholar]
  21. Kuijpers T. W., Mul E. P., Blom M., Kovach N. L., Gaeta F. C., Tollefson V., Elices M. J., Harlan J. M. Freezing adhesion molecules in a state of high-avidity binding blocks eosinophil migration. J Exp Med. 1993 Jul 1;178(1):279–284. doi: 10.1084/jem.178.1.279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Moser R., Fehr J., Olgiati L., Bruijnzeel P. L. Migration of primed human eosinophils across cytokine-activated endothelial cell monolayers. Blood. 1992 Jun 1;79(11):2937–2945. [PubMed] [Google Scholar]
  23. Mulligan M. S., Varani J., Warren J. S., Till G. O., Smith C. W., Anderson D. C., Todd R. F., 3rd, Ward P. A. Roles of beta 2 integrins of rat neutrophils in complement- and oxygen radical-mediated acute inflammatory injury. J Immunol. 1992 Mar 15;148(6):1847–1857. [PubMed] [Google Scholar]
  24. Noonan T. C., Gundel R. H., Desai S. N., Stearns C., Barton R. W., Rothlein R., Letts L. G., Piper P. J. The effects of an anti-CD18 antibody (R15.7) in antigen-induced airway hyperresponsiveness (AH) and cell influx in guinea pigs. Agents Actions. 1991 Sep;34(1-2):211–213. doi: 10.1007/BF01993282. [DOI] [PubMed] [Google Scholar]
  25. Nourshargh S., Rampart M., Hellewell P. G., Jose P. J., Harlan J. M., Edwards A. J., Williams T. J. Accumulation of 111In-neutrophils in rabbit skin in allergic and non-allergic inflammatory reactions in vivo. Inhibition by neutrophil pretreatment in vitro with a monoclonal antibody recognizing the CD18 antigen. J Immunol. 1989 May 1;142(9):3193–3198. [PubMed] [Google Scholar]
  26. Smith C. W., Marlin S. D., Rothlein R., Toman C., Anderson D. C. Cooperative interactions of LFA-1 and Mac-1 with intercellular adhesion molecule-1 in facilitating adherence and transendothelial migration of human neutrophils in vitro. J Clin Invest. 1989 Jun;83(6):2008–2017. doi: 10.1172/JCI114111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Teixeira M. M., Doenhoff M. J., McNeice C., Williams T. J., Hellewell P. G. Mechanisms of the inflammatory response induced by extracts of Schistosoma mansoni larvae in guinea pig skin. J Immunol. 1993 Nov 15;151(10):5525–5534. [PubMed] [Google Scholar]
  28. Teixeira M. M., Williams T. J., Hellewell P. G. E-type prostaglandins enhance local oedema formation and neutrophil accumulation but suppress eosinophil accumulation in guinea-pig skin. Br J Pharmacol. 1993 Sep;110(1):416–422. doi: 10.1111/j.1476-5381.1993.tb13826.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Tonnesen M. G., Anderson D. C., Springer T. A., Knedler A., Avdi N., Henson P. M. Adherence of neutrophils to cultured human microvascular endothelial cells. Stimulation by chemotactic peptides and lipid mediators and dependence upon the Mac-1, LFA-1, p150,95 glycoprotein family. J Clin Invest. 1989 Feb;83(2):637–646. doi: 10.1172/JCI113928. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Walsh G. M., Mermod J. J., Hartnell A., Kay A. B., Wardlaw A. J. Human eosinophil, but not neutrophil, adherence to IL-1-stimulated human umbilical vascular endothelial cells is alpha 4 beta 1 (very late antigen-4) dependent. J Immunol. 1991 May 15;146(10):3419–3423. [PubMed] [Google Scholar]
  31. Webster R. O., Hong S. R., Johnston R. B., Jr, Henson P. M. Biologial effects of the human complement fragments C5a and C5ades Arg on neutrophil function. Immunopharmacology. 1980 Jun;2(3):201–219. doi: 10.1016/0162-3109(80)90050-8. [DOI] [PubMed] [Google Scholar]
  32. Wedmore C. V., Williams T. J. Control of vascular permeability by polymorphonuclear leukocytes in inflammation. Nature. 1981 Feb 19;289(5799):646–650. doi: 10.1038/289646a0. [DOI] [PubMed] [Google Scholar]
  33. Weg V. B., Watson M. L., Cordeiro R. S., Williams T. J. Histamine, leukotriene D4 and platelet-activating factor in guinea pig passive cutaneous anaphylaxis. Eur J Pharmacol. 1991 Nov 5;204(2):157–163. doi: 10.1016/0014-2999(91)90700-z. [DOI] [PubMed] [Google Scholar]
  34. Weg V. B., Williams T. J., Lobb R. R., Nourshargh S. A monoclonal antibody recognizing very late activation antigen-4 inhibits eosinophil accumulation in vivo. J Exp Med. 1993 Feb 1;177(2):561–566. doi: 10.1084/jem.177.2.561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Wegner C. D., Gundel R. H., Reilly P., Haynes N., Letts L. G., Rothlein R. Intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of asthma. Science. 1990 Jan 26;247(4941):456–459. doi: 10.1126/science.1967851. [DOI] [PubMed] [Google Scholar]
  36. Weller P. F., Rand T. H., Goelz S. E., Chi-Rosso G., Lobb R. R. Human eosinophil adherence to vascular endothelium mediated by binding to vascular cell adhesion molecule 1 and endothelial leukocyte adhesion molecule 1. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7430–7433. doi: 10.1073/pnas.88.16.7430. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Williams T. J., Jose P. J. Mediation of increased vascular permeability after complement activation. Histamine-independent action of rabbit C5a. J Exp Med. 1981 Jan 1;153(1):136–153. doi: 10.1084/jem.153.1.136. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Williamson L. M., Sheppard K., Davies J. M., Fletcher J. Neutrophils are involved in the increased vascular permeability produced by activated complement in man. Br J Haematol. 1986 Oct;64(2):375–384. doi: 10.1111/j.1365-2141.1986.tb04131.x. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES