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Increase in vascular permeability induced by leukotriene b4 and the role of polymorphonuclear leukocytes

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Abstract

Leukotriene B4 (LTB4), a metabolite of arachidonic acid, is known to be a potent chemotactic and chemokinetic substance. We have used the hamster cheek pouch microcirculation model to study the effect of LTB4 on vascular permeability and the involvement of neutrophil granulocytes in this response. Intravascular fluorescein-labeled dextran (mol wt 150,000) was used as a tracer of macromolecular permeability. Topical application of LTB4 (150 nM-5 μM) to the hamster cheek pouch resulted in an immediate increase in adhering leukocytes in postcapillary venules and later larger venules. Leukocyte accumulation was reversible, but continued longer the higher the dose of LTB4 used. Subsequently, a dose-dependent increase in vascular permeability was seen at postcapillary and larger venules, with a maximum 10–20 min after application; the maximum occurred later the higher the dose of LTB4. Depletion of neutrophil granulocytes by pretreatment of the animals with antineutrophil serum obtained from immunized rabbits significantly decreased the permeability response to LTB4, whereas the response to histamine was unaffected. These results suggest that neutrophil granulocytes play a role in LTB4-mediated permeability increase. LTB4 may be of importance both for the leukocyte accumulation and for the edema formation seen in inflammatory reactions.

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References

  1. Borgeat, P., andB. Samuelsson. 1979. Arachidonic acid metabolism in polymorphonuclear leukocytes: Effect of ionophore A23187.Proc. Natl. Acad. Sci. U.S.A. 76:2148–2152.

    Google Scholar 

  2. Doig, M. V., andA. W. Ford-Hutchinson. 1980. The production and characterization of products of lipoxygenase enzyme systems released by rat peritoneal macrophages. Prostaglandins20:1004–1019.

    Google Scholar 

  3. Ford-Hutchinson, A. W., M. A. Bray, M. V. Doig, M. E. Shipley, andM. J. H. Smith. 1980. Leukotriene B, a potent chemokinetic and aggregating substance released from polymorphonuclear leukocytes.Nature 286:264–265.

    Google Scholar 

  4. Goetzl, E. J., andW. C. Pickett. 1980. The human PMN leukocyte chemotactic activity of complex hydroxy-eicosatetraenoic acids (HETEs).J. Immunol. 125:1789–1791.

    Google Scholar 

  5. Palmer, R. M. J., R. J. Stepney, G. A. Higgs, andK. E. Eakins. 1980. Chemokinetic activity of arachidonic acid lipoxygenase products on leucocytes of different species.Prostaglandins 20:411–418.

    Google Scholar 

  6. Malmsten, C. L., J. Palmblad, A.-M. UdÉn, O. Rådmark, L. Engstedt, andB. Samuel-Sson. 1980. Leukotriene B4: A highly potent and stereospecific factor stimulating migration of polymorphonuclear leukocytes.Acta Physiol. Scand. 110:449–451.

    Google Scholar 

  7. Smith, M. J. H., A. W. Ford-Hutchinson, andM. A. Bray. 1980. Leukotriene B: A potent mediator of inflammation.J. Pharm. Pharmacol. 32:517–518.

    Google Scholar 

  8. Björk, J., K.-E. Arfors, P. Hedqvist, S.-E. DahlÉn, J.-Å. Lindgren. 1982. Leukotriene B4 causes leukocyte migrationin vivo. European J Pharmacol.4 (Submitted).

  9. Wedmore, C. V., andT. J. Williams. 1981. Control of vascular permeability by polymorphonuclear leukocytes in inflammation.Nature 289:646–650.

    Google Scholar 

  10. Bray, M. A., F. M. Cunningham, A. W. Ford-Hutchinson, andM. J. H. Smith. 1981. Leukotriene4: A mediator of vascular permeability.Br. J. Pharmacol. 72:483–486.

    Google Scholar 

  11. Simpson, D. M., andR. Ross. 1971. Effects of heterologous antineutrophil serum in guinea pigs. Hematologic and ultrastructural observations.Am. J. Pathol. 65:79–102.

    Google Scholar 

  12. Karlsson, K.-A., andE. Thal. 1974. Studies on the detection of salmonellae in fishmeal by the direct and indirect immunofluorescent method.Nord. Vet. Med. 26:492–498.

    Google Scholar 

  13. 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 

  14. Svensjö, E., K.-E. Arfors, G. Arturson, andG. Rutili. 1978. The hamster cheek pouch preparation as a model for studies of macromolecular permeability of the microvasculature.Upsala J. Med. Sci. 83:71–79.

    Google Scholar 

  15. Svensjö, E., C. G. A. Persson, andG. Rutili. 1977. Inhibition of bradykinin induced macromolecular leakage from postcapillary venules by β2-adrenoreceptor stimulant, terbutaline.Acta Physiol, Scand. 101:504–506.

    Google Scholar 

  16. Del Maestro, R. F., J. Björk, andK.-E. Arfors. 1981. Increase in microvascular permeability induced by enzymatically generated free radicals. Part I. In vivo study.Microvasc. Res. 22:239–254.

    Google Scholar 

  17. Dahlén, 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 venues: In vivo effects with relevance to the acute inflammatory response.Proc. Natl. Acad. Sci. U.S.A. 78:3887–3891.

    Google Scholar 

  18. Ley, K., and K.-E.Arfors. 1982. Changes in macromolecular permeability by intravascular generation of oxygen derived free radicals.Microvasc. Res. (in press).

  19. Issekutz, A. C. 1981. Vascular responses during acute neutrophilic inflammation: Their relationship to in vivo neutrophil emigration.Lab. Invest. 45:435–441.

    Google Scholar 

  20. Joyner, W. L., E. SvensjÖ, andK.-E. Arfors. 1979. Simultaneous measurements of macomolecular leakage and arteriolar blood flow as altered by PGE1 and β2-receptor stimulant in the hamster cheek pouch.Microvasc. Res. 18:301–310.

    Google Scholar 

  21. Sacks, T., C. F., Moldow, P. R. Craddock, T. K. Bowers, andH. S. Jacob. 1978. Oxygen-radicals mediate endothelial cell damage by complement-stimulated granulocytes.J. Clin. Invest. 61:1161–1167.

    Google Scholar 

  22. Rae, S. A., andM. J. H. Smith. 1981. The stimulation of lysosomal enzyme secretion from human polymorphonuclear leukocytes by leukotriene B4.J. Pharm. Pharmacol. 33: 616–617.

    Google Scholar 

  23. Hafstrom, I., J. Palmblad, C. L. Malmsten, O. Rådmark, andB. Samuelsson. 1981. Leukotriene B4-a stereospecific stimulator for release of lysosomal enzymes from neutrophils.FEBS Lett. 130:146–148.

    Google Scholar 

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Authors and Affiliations

  1. Department of Experimental Medicine, Pharmacia AB, Uppsala, Sweden

    Jakob Björk & Karl-E. Arfors

  2. Department of Physiology, Karolinska Institutet, Stockholm, Sweden

    Per Hedqvist

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  1. Jakob Björk
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  2. Per Hedqvist
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  3. Karl-E. Arfors
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Björk, J., Hedqvist, P. & Arfors, KE. Increase in vascular permeability induced by leukotriene b4 and the role of polymorphonuclear leukocytes. Inflammation 6, 189–200 (1982). https://doi.org/10.1007/BF00916243

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