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Induction of Ocular Inflammation by Synthetic Mediators

Induction of Ocular Inflammation by Synthetic Mediators Abstract • Chemotactic mediators, N-formyl-methionyl-leucyl-phenylalanine (FMLP) and the complement component C5a, were injected into the rabbit cornea, vitreous, and skin to induce a reaction resembling the "Arthus phenomenon." Injection of these mediators induced edema and granulocytic infiltration in the cornea, conjunctiva, and skin. These histologic changes resembled the inflammation produced by antigen (ovalbumin [OVA]) in specifically immunized rabbits. Keratitis began after two hours and subsided six hours after the injection. Conversely, the vitreous response started six hours after injection of FMLP and C5a and peaked between 24 and 48 hours. All the inflammatory reactions induced by FMLP, C5a, and rechallenge with antigen could be inhibited in varying degrees by subconjunctival injection of 0.1 mL of 10-5M dexamethasone, quinacrine, 5,8,11,14-eicosatetraynoic acid (ETYA), or indomethacin, agents that suppress different sites of chemotaxis of polymorphonuclear leukocytes. However, only the inflammation induced by FMLP could be inhibited by carbobenzoxy-phe-met, a competitive inhibitor of FMLP. References 1. Leber T: Uber die Entstehung der entzündung und die Wirkung der ent zündungerregenden Shâdlichkeite . Fortschr Med 1888;6:460-464. 2. Boyum A: Isolation of mononuclear cells and granulocytes by one centrifugation and sedimentation at 1Xg . Scand J Clin Lab Invest 1968; 21( (suppl 97) ):77-89.Crossref 3. Gallin JI, Quie PG (eds): Leukocyte Chemotaxis: Methods, Physiology and Clinical Implications . New York, Raven Press, 1978. 4. Schiffmann E, Corcoran B, Wahl SM: N-formyl-methionyl peptides as attractants for leucocytes . Proc Natl Acad Sci 1975;71:1059-1062.Crossref 5. Valone FH: Modulation of human neutrophils and eosinophil leukocyte chemotaxis . Clin Immunol Immunopathol 1980;15:52-64.Crossref 6. Niedel JE, Kahane I, Cuatrecasas P: Receptor-mediated internalization of fluorescent chemotactic peptide by human neutrophils . Science 1979;205:1412-1414.Crossref 7. Williams LT, Snyderman R, Pike MC, et al: Specific receptor sites for chemotactic peptide on human polymorphonuclear leukocytes . Proc Natl Acad Sci 1977;74:1204-1208.Crossref 8. Aswanikumar S, Corcoran B, Schiffmann E, et al: Demonstration of receptor on rabbit neutrophils for chemotactic peptide . Biochem Biophys Res Commun 1977;74:810-817.Crossref 9. Snyderman R, Fudman E: Demonstration of a chemotactic factor receptor on macrophages . J Immunol 1980;124:2754-2757. 10. Schiffmann E, Showell HJ, Corcoran BA, et al: The isolation and partial characterization of neutrophil chemotactic factors from E coli . J Immunol 1975;114:1831-1837. 11. Schiffmann E, Corcoran BA, Aswanikumar S: Molecular events in the reponse of neutrophils to synthetic N-f-Met chemotactic peptides: Demonstration of a specific receptor for leukocyte chemotaxis , in Gallin JI, Quie PD (eds): Leukocyte Chemotaxis: Methods, Physiology and Clinical Implications . New York, Raven Press, 1978, pp 97-111. 12. Simchowitz L, Spilberg I: Chemotactic factor-induced generation of superoxide radicals by human neutrophils: Evidence for the role of sodium . J Immunol 1979;123:2428-2435. 13. Becker EL: Some inter-relations of neutrophil chemotaxis lysosomal enzyme secretion and phagocytosis as revealed by synthetic peptides . Am J Pathol 1976;85:385-389. 14. O'Flaherty JT, Showell HJ, Becker EL, et al: Substances which aggregate neutrophils: Mechanism of action . Am J Pathol 1978;92:155-166. 15. Desai V, Kreutzer DL, Showell HJ, et al: Acute inflammatory pulmonary reaction induced by chemotactic factors . Am J Pathol 1979;96:71-84. 16. Hirata F, Corcoran BA, Venkatasubramaniam K, et al: Chemoattractants stimulate degradation of methylated phospholipids and release arachidonic acid in rabbit leukocytes . Proc Natl Acad Sci 1979;76:2640-2643.Crossref 17. Chenoweth DE, Hugli TE: Demonstration of a specific receptor for C5a on human neutrophils . Proc Natl Acad Sci 1978;75:3943-3947.Crossref 18. Fernandez NH, Henson PM, Otani A, et al: Chemotactic response to human C3a and C5a anaphylatoxins: I. Evaluation of C3a and C5a leukotaxis in vitro and under simulated in vivo conditions . J Immunol 1978;120:109-115. 19. Burky EL: Relation of ocular sensitivity of the 'Arthus phenomenon' in the rabbit . Arch Ophthalmol 1933;10:368-374.Crossref 20. Okada M, Shimada K: Effect of various pharmacologic agents on allergic inflammation of the eye . Invest Ophthalmol Vis Sci 1980;19:176-181. 21. Abelson MB, Allansmith MR: Histamine and the eye , in Silverstein AM, O'Connor GR (eds): Immunology and Immunopathology of the Eye . New York, Masson Publishing Co, 1978, pp 362-364. 22. Miller RL, Melmon KL: The related roles of histamine, serotonin and bradykinin in the pathogenesis of inflammation . Semin Hematol 1970;3:5-38. 23. Ambache N, Karanagh L, Whiting G: Effect of mechanical stimulation on rabbit's eye release of active substance in anterior chamber perfusates . J Physiol 1965;176:378-408. 24. Issekutz AC, Movat HZ: The in vivo quantitation and kinetics of rabbit neutrophil leukocyte accumulation in the skin in response to chemotactic agents and E coli . Lab Invest 1980;42:130-137. 25. Garbner G, Boltz G, Forster O: Macrophage-like properties of human hyalocytes . Invest Ophthalmol Vis Sci 1980;19:333-340. 26. Showell HJ, Freer RJ, Zigmond SH, et al: The structure activity relations of synthetic peptides as chemotactic factors and inducers of lysosomal enzyme secretion for neutrophils . J Exp Med 1976;143:1154-1169.Crossref 27. Marasco WA, Becker EL, Oliver JM: The ionic basis of chemotaxis . Am J Pathol 1980; 98:749-766. 28. Pike M, Snyderman R: Lipid requirement for leukocyte chemotaxis and phagocytosis effect of inhibitors of phospholipid and cholesterol synthesis . J Immunol 1980;124:1963-1968. 29. O'Dea RF, Viveros DH, Axelrod J, et al: Rapid stimulation of protein carboxymethylation in leukocytes by a chemotactic peptide . Nature 1978;272:462-464.Crossref 30. Phan SH, Ward PA: Generation of biologic activity from the purified α-chain of C5 . J Immunol 1979;123:2735-2740. 31. O'Flaherty JT, Showell HJ, Ward PA, et al: A possible role of arachidonic acid in human neutrophil aggregation and degeneration . Am J Pathol 1979;96:799-810. 32. O'Flaherty JT, Showell HJ, Kreitzer DL, et al: Inhibition of in vivo and in vitro neutrophil responses to chemotactic factors by a competitive antagonist . J Immunol 1978;120:1326-1332. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Ophthalmology American Medical Association

Induction of Ocular Inflammation by Synthetic Mediators

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References (36)

Publisher
American Medical Association
Copyright
Copyright © 1981 American Medical Association. All Rights Reserved.
ISSN
0003-9950
eISSN
1538-3687
DOI
10.1001/archopht.1981.03930020310024
Publisher site
See Article on Publisher Site

Abstract

Abstract • Chemotactic mediators, N-formyl-methionyl-leucyl-phenylalanine (FMLP) and the complement component C5a, were injected into the rabbit cornea, vitreous, and skin to induce a reaction resembling the "Arthus phenomenon." Injection of these mediators induced edema and granulocytic infiltration in the cornea, conjunctiva, and skin. These histologic changes resembled the inflammation produced by antigen (ovalbumin [OVA]) in specifically immunized rabbits. Keratitis began after two hours and subsided six hours after the injection. Conversely, the vitreous response started six hours after injection of FMLP and C5a and peaked between 24 and 48 hours. All the inflammatory reactions induced by FMLP, C5a, and rechallenge with antigen could be inhibited in varying degrees by subconjunctival injection of 0.1 mL of 10-5M dexamethasone, quinacrine, 5,8,11,14-eicosatetraynoic acid (ETYA), or indomethacin, agents that suppress different sites of chemotaxis of polymorphonuclear leukocytes. However, only the inflammation induced by FMLP could be inhibited by carbobenzoxy-phe-met, a competitive inhibitor of FMLP. References 1. Leber T: Uber die Entstehung der entzündung und die Wirkung der ent zündungerregenden Shâdlichkeite . Fortschr Med 1888;6:460-464. 2. Boyum A: Isolation of mononuclear cells and granulocytes by one centrifugation and sedimentation at 1Xg . Scand J Clin Lab Invest 1968; 21( (suppl 97) ):77-89.Crossref 3. Gallin JI, Quie PG (eds): Leukocyte Chemotaxis: Methods, Physiology and Clinical Implications . New York, Raven Press, 1978. 4. Schiffmann E, Corcoran B, Wahl SM: N-formyl-methionyl peptides as attractants for leucocytes . Proc Natl Acad Sci 1975;71:1059-1062.Crossref 5. Valone FH: Modulation of human neutrophils and eosinophil leukocyte chemotaxis . Clin Immunol Immunopathol 1980;15:52-64.Crossref 6. Niedel JE, Kahane I, Cuatrecasas P: Receptor-mediated internalization of fluorescent chemotactic peptide by human neutrophils . Science 1979;205:1412-1414.Crossref 7. Williams LT, Snyderman R, Pike MC, et al: Specific receptor sites for chemotactic peptide on human polymorphonuclear leukocytes . Proc Natl Acad Sci 1977;74:1204-1208.Crossref 8. Aswanikumar S, Corcoran B, Schiffmann E, et al: Demonstration of receptor on rabbit neutrophils for chemotactic peptide . Biochem Biophys Res Commun 1977;74:810-817.Crossref 9. Snyderman R, Fudman E: Demonstration of a chemotactic factor receptor on macrophages . J Immunol 1980;124:2754-2757. 10. Schiffmann E, Showell HJ, Corcoran BA, et al: The isolation and partial characterization of neutrophil chemotactic factors from E coli . J Immunol 1975;114:1831-1837. 11. Schiffmann E, Corcoran BA, Aswanikumar S: Molecular events in the reponse of neutrophils to synthetic N-f-Met chemotactic peptides: Demonstration of a specific receptor for leukocyte chemotaxis , in Gallin JI, Quie PD (eds): Leukocyte Chemotaxis: Methods, Physiology and Clinical Implications . New York, Raven Press, 1978, pp 97-111. 12. Simchowitz L, Spilberg I: Chemotactic factor-induced generation of superoxide radicals by human neutrophils: Evidence for the role of sodium . J Immunol 1979;123:2428-2435. 13. Becker EL: Some inter-relations of neutrophil chemotaxis lysosomal enzyme secretion and phagocytosis as revealed by synthetic peptides . Am J Pathol 1976;85:385-389. 14. O'Flaherty JT, Showell HJ, Becker EL, et al: Substances which aggregate neutrophils: Mechanism of action . Am J Pathol 1978;92:155-166. 15. Desai V, Kreutzer DL, Showell HJ, et al: Acute inflammatory pulmonary reaction induced by chemotactic factors . Am J Pathol 1979;96:71-84. 16. Hirata F, Corcoran BA, Venkatasubramaniam K, et al: Chemoattractants stimulate degradation of methylated phospholipids and release arachidonic acid in rabbit leukocytes . Proc Natl Acad Sci 1979;76:2640-2643.Crossref 17. Chenoweth DE, Hugli TE: Demonstration of a specific receptor for C5a on human neutrophils . Proc Natl Acad Sci 1978;75:3943-3947.Crossref 18. Fernandez NH, Henson PM, Otani A, et al: Chemotactic response to human C3a and C5a anaphylatoxins: I. Evaluation of C3a and C5a leukotaxis in vitro and under simulated in vivo conditions . J Immunol 1978;120:109-115. 19. Burky EL: Relation of ocular sensitivity of the 'Arthus phenomenon' in the rabbit . Arch Ophthalmol 1933;10:368-374.Crossref 20. Okada M, Shimada K: Effect of various pharmacologic agents on allergic inflammation of the eye . Invest Ophthalmol Vis Sci 1980;19:176-181. 21. Abelson MB, Allansmith MR: Histamine and the eye , in Silverstein AM, O'Connor GR (eds): Immunology and Immunopathology of the Eye . New York, Masson Publishing Co, 1978, pp 362-364. 22. Miller RL, Melmon KL: The related roles of histamine, serotonin and bradykinin in the pathogenesis of inflammation . Semin Hematol 1970;3:5-38. 23. Ambache N, Karanagh L, Whiting G: Effect of mechanical stimulation on rabbit's eye release of active substance in anterior chamber perfusates . J Physiol 1965;176:378-408. 24. Issekutz AC, Movat HZ: The in vivo quantitation and kinetics of rabbit neutrophil leukocyte accumulation in the skin in response to chemotactic agents and E coli . Lab Invest 1980;42:130-137. 25. Garbner G, Boltz G, Forster O: Macrophage-like properties of human hyalocytes . Invest Ophthalmol Vis Sci 1980;19:333-340. 26. Showell HJ, Freer RJ, Zigmond SH, et al: The structure activity relations of synthetic peptides as chemotactic factors and inducers of lysosomal enzyme secretion for neutrophils . J Exp Med 1976;143:1154-1169.Crossref 27. Marasco WA, Becker EL, Oliver JM: The ionic basis of chemotaxis . Am J Pathol 1980; 98:749-766. 28. Pike M, Snyderman R: Lipid requirement for leukocyte chemotaxis and phagocytosis effect of inhibitors of phospholipid and cholesterol synthesis . J Immunol 1980;124:1963-1968. 29. O'Dea RF, Viveros DH, Axelrod J, et al: Rapid stimulation of protein carboxymethylation in leukocytes by a chemotactic peptide . Nature 1978;272:462-464.Crossref 30. Phan SH, Ward PA: Generation of biologic activity from the purified α-chain of C5 . J Immunol 1979;123:2735-2740. 31. O'Flaherty JT, Showell HJ, Ward PA, et al: A possible role of arachidonic acid in human neutrophil aggregation and degeneration . Am J Pathol 1979;96:799-810. 32. O'Flaherty JT, Showell HJ, Kreitzer DL, et al: Inhibition of in vivo and in vitro neutrophil responses to chemotactic factors by a competitive antagonist . J Immunol 1978;120:1326-1332.

Journal

Archives of OphthalmologyAmerican Medical Association

Published: Aug 1, 1981

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