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.
Similar content being viewed by others
References
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.
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.
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.
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.
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.
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.
Lewis, R. E., andH. J. Granger. 1986. Neutrophil-dependent mediation of microvascular permeability.Fed. Proc. 45:109–113.
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.
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.
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).
Duling, B. R. 1973. The preparation and use of the hamster cheek pouch for studies of the microcirculation.Microvasc. Res. 5:423–429.
Svensjö, E. 1978. Bradykinin and prostaglandin E1, E2 and F2α-induced macromolecular leakage in the hamster cheek pouch.Prostaglandins Med. 1:397–410.
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.
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.
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.
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.
Davis, M. J. 1988. Control of bat wing capillary pressure and blood flow during reduced perfusion pressure.Am. J. Physiol. 255:H1114-H1129.
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.
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.
Rosengren, S., J. Björk, G. Smedegård. 1988. Oxygen radicals are not a prerequisite for neutrophil-mediated increased vascular permeability.Lab. Invest. 58:559–564.
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.
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.
Raud, J. 1989. Intravital microscopic studies on acute mast cell-dependent inflammation.Acta Physiol. Scand. 135(Suppl. 578):1–57.
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.
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.
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.
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.
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.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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
Issue Date:
DOI: https://doi.org/10.1007/BF00914313