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. 1994 Sep;113(1):117–120. doi: 10.1111/j.1476-5381.1994.tb16182.x

Effect of in vivo desensitization to leukotriene B4 on eosinophil infiltration in response to C5a in guinea-pig skin.

E R Pettipher 1, E D Salter 1, H J Showell 1
PMCID: PMC1510040  PMID: 7812600

Abstract

1. The effect of in vivo desensitization to leukotriene B4 (LTB4) on eosinophil infiltration in response to recombinant C5a was examined in guinea-pig skin. 2. LTB4 (10-300 ng) and C5a (1-10 micrograms) caused a dose-dependent increase in the levels of eosinophil peroxidase activity (a measure of eosinophil infiltration) 4 h after injection into guinea-pig skin. Leukotriene B4 and C5a were approximately equipotent on a molar basis. Platelet activating factor (0.01-10 micrograms) also caused eosinophil accumulation but was much less active than LTB4 or C5a. 3. 20-Hydroxy-LTB4 caused a dose-dependent desensitization of eosinophil responses to LTB4 (ED50 = 1.6 micrograms kg-1, s.c.) and partially reduced responses to C5a. At a dose of 20-hydroxy-LTB4 (10 micrograms) which inhibited responses to LTB4 completely, responses to C5a were reduced by 56.5 +/- 1.8% (n = 5). The structurally related metabolite of 20-hydroxy-LTB4, 20-carboxy-LTB4, which does not cause desensitization to the effects of LTB4, did not inhibit eosinophil infiltration in response to C5a. 4. The LTB4 receptor antagonist, SC-41,930 (10 mg kg-1, p.o.), also inhibited eosinophil accumulation in response to C5a by 63.0 +/- 3.9% (n = 5) at a dose which inhibited responses to LTB4 by 86.5 +/- 1.9% (n = 5). 5. These data indicate that eosinophil infiltration in response to C5a may, in part, be mediated by the generation of secondary chemotactic factors such as LTB4.

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Selected References

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  1. Baggiolini M., Walz A., Kunkel S. L. Neutrophil-activating peptide-1/interleukin 8, a novel cytokine that activates neutrophils. J Clin Invest. 1989 Oct;84(4):1045–1049. doi: 10.1172/JCI114265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cheng J. B., Pillar J. S., Shirley J. T., Showell H. J., Watson J. W., Cohan V. L. Antigen-mediated pulmonary eosinophilia in immunoglobulin G1-sensitized guinea pigs: eosinophil peroxidase as a simple specific marker for detecting eosinophils in bronchoalveolar lavage fluid. J Pharmacol Exp Ther. 1993 Feb;264(2):922–929. [PubMed] [Google Scholar]
  3. 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]
  4. Cramer R., Soranzo M. R., Dri P., Menegazzi R., Pitotti A., Zabucchi G., Patriarca P. A simple reliable assay for myeloperoxidase activity in mixed neutrophil-eosinophil cell suspensions: application to detection of myeloperoxidase deficiency. J Immunol Methods. 1984 May 11;70(1):119–125. doi: 10.1016/0022-1759(84)90396-x. [DOI] [PubMed] [Google Scholar]
  5. Czarnetzki B. M., Mertensmeier R. In vitro and in vivo chemotaxis of guinea pig leukocytes toward leukotriene B4 and its w-oxidation products. Prostaglandins. 1985 Jul;30(1):5–11. doi: 10.1016/s0090-6980(85)80006-x. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Fretland D. J., Widomski D. L., Zemaitis J. M., Walsh R. E., Levin S., Djuric S. W., Shone R. L., Tsai B. S., Gaginella T. S. Inflammation of guinea pig dermis. Effects of leukotriene B4 receptor antagonist, SC-41930. Inflammation. 1990 Dec;14(6):727–739. doi: 10.1007/BF00916375. [DOI] [PubMed] [Google Scholar]
  8. Gleich G. J. The eosinophil and bronchial asthma: current understanding. J Allergy Clin Immunol. 1990 Feb;85(2):422–436. doi: 10.1016/0091-6749(90)90151-s. [DOI] [PubMed] [Google Scholar]
  9. Håkansson L., Westerlund D., Venge P. New method for the measurement of eosinophil migration. J Leukoc Biol. 1987 Dec;42(6):689–696. doi: 10.1002/jlb.42.6.689. [DOI] [PubMed] [Google Scholar]
  10. Kameyoshi Y., Dörschner A., Mallet A. I., Christophers E., Schröder J. M. Cytokine RANTES released by thrombin-stimulated platelets is a potent attractant for human eosinophils. J Exp Med. 1992 Aug 1;176(2):587–592. doi: 10.1084/jem.176.2.587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Pettipher E. R., Salter E. D., Breslow R., Raycroft L., Showell H. J. Specific inhibition of leukotriene B4 (LTB4)-induced neutrophil emigration by 20-hydroxy LTB4: implications for the regulation of inflammatory responses. Br J Pharmacol. 1993 Sep;110(1):423–427. doi: 10.1111/j.1476-5381.1993.tb13827.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Richards I. M., Griffin R. L., Oostveen J. A., Morris J., Wishka D. G., Dunn C. J. Effect of the selective leukotriene B4 antagonist U-75302 on antigen-induced bronchopulmonary eosinophilia in sensitized guinea pigs. Am Rev Respir Dis. 1989 Dec;140(6):1712–1716. doi: 10.1164/ajrccm/140.6.1712. [DOI] [PubMed] [Google Scholar]
  13. Schall T. J. Biology of the RANTES/SIS cytokine family. Cytokine. 1991 May;3(3):165–183. doi: 10.1016/1043-4666(91)90013-4. [DOI] [PubMed] [Google Scholar]
  14. Sehmi R., Rossi A. G., Kay A. B., Cromwell O. Identification on receptors for leukotriene B4 expressed on guinea-pig peritoneal eosinophils. Immunology. 1992 Sep;77(1):129–135. [PMC free article] [PubMed] [Google Scholar]
  15. Simmons P. M., Salmon J. A., Moncada S. The release of leukotriene B4 during experimental inflammation. Biochem Pharmacol. 1983 Apr 15;32(8):1353–1359. doi: 10.1016/0006-2952(83)90446-x. [DOI] [PubMed] [Google Scholar]
  16. Strath M., Warren D. J., Sanderson C. J. Detection of eosinophils using an eosinophil peroxidase assay. Its use as an assay for eosinophil differentiation factors. J Immunol Methods. 1985 Nov 7;83(2):209–215. doi: 10.1016/0022-1759(85)90242-x. [DOI] [PubMed] [Google Scholar]
  17. Wardlaw A. J., Moqbel R., Cromwell O., Kay A. B. Platelet-activating factor. A potent chemotactic and chemokinetic factor for human eosinophils. J Clin Invest. 1986 Dec;78(6):1701–1706. doi: 10.1172/JCI112765. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Yeadon M., Dougan F. L., Petrovic A., Beesley J. E., Payne A. N. Effect of BW B70C, a novel inhibitor of arachidonic acid 5-lipoxygenase, on allergen-induced bronchoconstriction and late-phase lung eosinophil accumulation in sensitised guinea-pigs. Agents Actions. 1993 Jan;38(1-2):8–18. doi: 10.1007/BF02027207. [DOI] [PubMed] [Google Scholar]

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