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Leukotriene B4-induced permeability increase in postcapillary venules and its inhibition by three different antiinflammatory drugs

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Abstract

Leukotriene B4 (LTB4) is a potent chemotactic and chemokinetic substance that causes leukocyte accumulation and increases vascular permeability. We have used the hamster cheek pouch model to study the effect of some different antiinflammatory drugs on the LTB4-induced microvascular permeability. Intravascular fluorescein-labeled dextran (mol wt 150,000) was used as a tracer of macromolecular leakage, which was measured as the number of venular leaky sites and as efflux of the vascular tracer. Topical application of LTB4 (10−8 M, 5 min) resulted in a reversible increase of the vascular permeability and could be repeated with 40-min intervals without any significant reduction in permeability response. The LTB4-induced response could be inhibited by budesonide (a glucocorticoid) given locally, by iloprost (a prostacyclin analog) given intravenously and by a combined local and intravenous treatment with terbutaline (aβ 2-receptor agonist) but not by local terbutaline treatment only.

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References

  1. Fräki, J. E., L. Jakoi, A. O. Davies, R. J. Lefkowitz, R. Snyderman, andG. S. Lazarus. 1983. Polymorphonuclear leukocyte function in psoriasis: Chemotaxis, chemokinesis, betaadrenergic receptors, and proteolytic enzymes of polymorphonuclear leukocytes in the peripheral blood from psoriatic patients.J. Invest. Dermatol. 81:254–257.

    Google Scholar 

  2. Lee, C. T., A. M. Fein, M. Lippmann, H. Holtzman, P. Kimbel, andG. Weinbaum. 1981. Elastolytic activity in pulmonary lavage fluid from patients with adult respiratory-distress syndrome.N. Engl. J. Med. 304:192–196.

    Google Scholar 

  3. Zimmerman, J. J., J. H. Shelhamer, andJ. E. Parrillo. 1985. Quantitative analysis of polymorphonuclear leukocyte superoxide anion generation in critically ill children.Crit. Care Med. 13:143–150.

    Google Scholar 

  4. Mullane, K. M., W. Westlin, andR. Kraemer. 1988. Activated neutrophils release mediators that may contribute to myocardial injury and dysfunction associated with ischemia and reperfusion.Ann. N.Y. Acad. Sci. 524:103–121.

    Google Scholar 

  5. Dahlen, S.-E., J. Björk, P. Hedqvist, K.-E. Arfors, S. Hammarström, J.-Å. Lindgren, andB. Samuelsson. 1981. Leukotrienes promote plasma leakage and leukocyte adhesion in postcapillary venules: In vivo effects with relevance to the acute inflammatory response.Proc. Natl. Acad. Sci. U.S.A. 78:3887–3891.

    Google Scholar 

  6. Björk, J., andG. Smedegård. 1987. Immune-complex-induced inflammatory reaction studied by intervital microscopy: Role of histamine and arachidonic acid metabolites.Inflammation 11:47–58.

    Google Scholar 

  7. Lewis, R. E., andH. J. Granger. 1986. Neutrophil-dependent mediation of microvascular permeability.Fed. Proc. 45:109–113.

    Google Scholar 

  8. Björk, J., andK.-E. Arfors. 1982. Oxygen free radicals and leukotriene B4 induced increase in vascular leakage is mediated by polymorphonuclear leukocytes.Agents Actions, Suppl. 11:63–72.

    Google Scholar 

  9. Persson, N. H., M. Erlansson, D. Bergqvist, R. Takolander, andE. Svensjö. 1987. Terbutaline and budesonide as inhibitors of postischaemic permeability increase.Acta Physiol. Scand. 129:517–524.

    Google Scholar 

  10. Erlansson, M., D. Bergqvist, N. H. Persson, andE. Svensjö. 1987. Modulation of ischemia and histamine induced macromolecular permeability increase in the hamster by a stable prostacyclin analogue (iloprost).Int. J. Microcirc. Clin. Exp. 6:183 (abstract).

    Google Scholar 

  11. Duling, B. R. 1973. The preparation and use of the hamster cheek pouch for studies of the microcirculation.Microvasc. Res. 5:423–429.

    Google Scholar 

  12. Svensjö, E. 1978. Bradykinin and prostaglandin E1, E2 and F-induced macromolecular leakage in the hamster cheek pouch.Prostaglandins Med. 1:397–410.

    Google Scholar 

  13. Jeppsson, A.-B., U. Johansson, andB. Waldeck. 1984. Steric aspects of agonism and antagonism atβ-adrenoceptors: Experiments with the enantiomers of terbutaline and pindolol.Acta Pharmacol. Toxicol. 54:285–291.

    Google Scholar 

  14. Svensjö, E., andW. L. Joyner. 1984. The effects of intermittent and continuous stimulation of microvessels in the cheek pouch of hamsters with histamine and bradykinin on the development of venular leaky sites.Microcirc. Endothel. Lymphatics 1:381–396.

    Google Scholar 

  15. Persson, N. H., M. Erlansson, E. SvensjÖ, R. Takolander, andD. Bergqvist. 1985. The hamster cheek pouch-an experimental model to study postischemic macromolecular permeability.Int. J. Microcirc. Clin. Exp. 4:257–263.

    Google Scholar 

  16. Svensjö, E., andK. Roempke. 1984. Microvascular aspects of oedema formation and its inhibition byβ 2-receptor stimulants and some other anti-inflammatory drugs.In Progress in Microcirculation Research, II. F. C. Courtice, D. G. Garlick, and M. A. Perry, editors. Committee in Postgraduate Medical Education, University of NSW, Sydney. 449–463.

    Google Scholar 

  17. Davis, M. J. 1988. Control of bat wing capillary pressure and blood flow during reduced perfusion pressure.Am. J. Physiol. 255:H1114-H1129.

    Google Scholar 

  18. Björk, J., P. Hedqvist, andK.-E. Arfors. 1982. Increase in vascular permeability induced by leukotriene B4 and the role of polymorphonuclear leukocytes.Inflammation 6:189–200.

    Google Scholar 

  19. Dunham, B., H. B. Hechtman, C. R. Valeri, andD. Shepro. 1984. Antiinflammatory agents inhibit microvascular permeability induced by leukotrienes and by stimulated human neutrophils.Microcirc. Endothel. Lymphatics 1:465–489.

    Google Scholar 

  20. Rosengren, S., J. Björk, G. Smedegård. 1988. Oxygen radicals are not a prerequisite for neutrophil-mediated increased vascular permeability.Lab. Invest. 58:559–564.

    Google Scholar 

  21. Lewis, R. E., andH. J. Granger. 1988. Diapedesis and the permeability of venous microvessels to protein macromolecules: The impact of leukotriene B4 (LTB4).Microcirc. Res. 35:27–47.

    Google Scholar 

  22. Rampart, M., andT. J. Williams. 1986. Polymorphonuclear leukocyte-dependent plasma-leakage in the rabbit skin is enhanced or inhibited by prostacyclin.Am. J. Pathol. 124:66–73.

    Google Scholar 

  23. Raud, J. 1989. Intravital microscopic studies on acute mast cell-dependent inflammation.Acta Physiol. Scand. 135(Suppl. 578):1–57.

    Google Scholar 

  24. Klausner, J. M., I. S. Paterson, C. R. Valeri, D. Shepro, andH. B. Hechtman. 1988. Limb ischemia-induced increase in permeability is mediated by leukocytes and leukotrienes.Ann. Surg. 208:755–760.

    Google Scholar 

  25. Mack, J. A., C. P. Nielson, D. L. Stevens, andR. E. Vestal. 1986.β-Adrenoceptormediated modulation of calcium ionophore activated polymorphonuclear leukocytes.Br. J. Pharmacol. 88:417–423.

    Google Scholar 

  26. Schrör, K., R. Ohlendorf, andH. Darius. 1981. Beneficial effects of a new carbacyclin derivative, ZK36374, in acute myocardial ischemia.J. Pharmacol. Exp. Ther. 219:243–249.

    Google Scholar 

  27. Müller, B., M. Schmidtke, andW. Witt. 1987. Action of the stable prostacyclin analogue iloprost on microvascular tone and permeability in the hamster cheek pouch.Prostaglandins Leukotrienes Med. 29:187–198.

    Google Scholar 

  28. Svensjö, E., andK. Roempke. 1985. Time-dependent inhibition of bradykinin- and histamineinduced microvascular permeability increase by local glucocorticoid treatment.Prog. Respir. Res. 19:173–180.

    Google Scholar 

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Erlansson, M., Svensjö, E. & Bergqvist, D. Leukotriene B4-induced permeability increase in postcapillary venules and its inhibition by three different antiinflammatory drugs. Inflammation 13, 693–705 (1989). https://doi.org/10.1007/BF00914313

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