Abstract
⊎ Background: Chicken egg white ovomacroglobulin (ovoM) is a potent protease inhibitor with broad-spectrum activity against various proteases. The combined effects of ovoM and the new quinolone, ofloxacin (OFLX) on experimental Pseudomonas aeruginosa keratitis were investigated. ⊎ Methods: The in vitro inhibitory effects of ovoM on protease activity in culture fluid of clinically isolated P. aeruginosa and on activity of human neutrophil elastase and cathepsin G were assayed using azo-casein as substrate. Albino rabbits received intrastromal injection of the isolated Pseudomonas strain (1 × 105 colony-forming units). At 16 h after inoculation, three treatment groups -0.1% ovoM alone, 0.3% OFLX alone, and a combination of both —and a non-treatment control group were tested. ⊎ Results: Protease activity in the culture solution and human neutrophil elastase was inhibited by ovoM, whereas cathepsin G was not inhibited effectively. In vivo additive therapeutic effects of ovoM and OFLX were observed at 96 h (P < 0.05 compared with OFLX alone). ⊎ Conclusion: The results indicate that inhibition of proteolytic activity with ovoM is useful in preventing stromal degradation in P. aeruginosa keratitis.
Similar content being viewed by others
References
Bohigian JG, Valenton M, Lejeune C, Okumoto M (1974) Collagenase inhibitor in Pseudomonas keratitis. Arch Ophthalmol 91:52–56
Brown SI (1975) Mooren's ulcer. Br J Ophthalmol 59:670–674
Chusid MJ, Davis SD (1985) Polymorphonuclear leukocyte kinetics in experimental induced keratitis. Arch Ophthalmol 103:270–274
Ellison A, Poirier R (1976) Therapeutic effects of heparin on Pseudomonas induced corneal ulceration. Am J Ophthalmol 82:619–627
Heck LW, Morihara K, McRae WB, Miller EJ (1986) Specific cleavage of human type III and IV collagen by Pseudomonas aeruginosa elastase. Infect Immun 51:115–118
Iglewski BH, Burns RP, Gipson IK (1977) Pathogenesis of corneal damage from Pseudomonas exotoxin A. Invest Ophthalmol Vis Sci 16:73–76
Ikai A, Kitamoto T, Nishigai M (1983) Alpha-2-macroglobulin like protease inhibitor from the egg white of Cubian crocodile (Crocodylus rhombifer). J Biochem 93:121–127
Ikai A, Hiri H, Sutoh H, Kikuchi M, Nagai Y (1985) Inhibition pattern of metalloprotease by ovomacroglobulin of Crocodylus rhombifer. Comp Biochem Physiol 80:209–211
Kamata R, Matsumoto K, Okamura R, Yamamoto T, Maeda H (1985) The Serratia 56K protease as a major pathogenic factor in serratial keratitis. Ophthalmology 92:1452–1459
Kamata R, Yamamoto T, Matsumoto K, Maeda H (1985) A serratial protease causes vascular permeability reaction by activation of the Hageman factor-dependent pathway in guinea pigs. Infect Immun 48:747–753
Kamata R, Miyagawa S, Maeda H, Okamura R (1991) Effects of topical chicken egg white ovomacroglobulin, a protease inhibitor, in severe peripheral corneal ulcers. (In Japanese) Rinsho Ganka 45:233–237
Kawaharajo K, Homma JY, Aoyagi T, Umezawa H (1982) Effect of phosphoramidon on protection against corneal ulcer caused by elastase and protease from Pseudomonas aeruginosa. Jpn J Exp Med 52:271–272
Kitamoto T, Nakashima M, Ikai A (1982) Hen egg white ovomacroglobulin has a protease inhibitory activity. J Biochem 92:1679–1682
Kreger AS, Gray ID (1978) Purification of Pseudomonas aeruginosa protease and microscopic characterization of pseudomonal protease-induced corneal damage. Infect Immun 19:630–648
Laibson PR (1972) Cornea and sclera. Arch Ophthalmol 88:553–574
Lass JH, Haaf J, Foster CF, Belcher C (1981) Visual outcome in eight cases of Serratia marcescens keratitis. Am J Ophthalmol 92:384–390
Lemp MA, Blackman HJ, Wilson LA, Leveille AS (1984) Gram-negative corneal ulcer in elderly aphakic eyes with extended wear lenses. Ophthalmology 91:60–63
Maeda H, Molla A (1989) Pathogenic potentials of bacterial proteases. Clin Chim Acta 185:368–375
Maeda H, Molla A, Oda T, Katsuki T (1987) Internalization of serratial protease into cells as an enzyme-inhibitor complex with α2-macroglobulin and regeneration of protease activity and cytotoxicity. J Biol Chem 262:10946–10950
Matsumoto K, Yamamoto T, Kamata R, Maeda H (1984) Pathogenesis of serratial infection: activation of the Hageman factor-prekallikrein cascade by serratial proteases. J Biochem 96:739–749
Miyagawa S, Nishino N, Kamata R, Okamura R, Maeda H (1991) Effects of protease inhibitors on growth of Serratia mareescens and Pseudomonas aeruginosa. Microb Pathogenesis 11:137–141
Miyagawa S, Kamata R, Matsumoto K, Okamura R, Maeda H (1991) Inhibitory effects of ovomacroglobulin on bacterial keratitis in rabbits. Graefe's Arch Clin Exp Ophthalmol 229:281–286
Molla A, Oda T, Maeda H (1987) Different binding kinetics of Serratia 56K protease with plasma α2-macroglobulin and chicken egg white ovomacroglobulin. J Biochem 101:199–205
Molla A, Matsumura Y, Yamamoto T, Okamura R, Maeda H (1987) Pathogenic capacity of proteases from Serratia marcescens and Pseudomonas aeruginosa and their suppression by chicken egg white ovomacroglobulin. Infect Immun 55:2509–2517
Molla A, Kagimoto T, Maeda H (1988) Cleavage of immunoglobulin G (Ig G) and Ig A around the hinge region by protease from Serratia marcescens. Infect Immun 55:916–920
Molla A, Tanase S, Hong YH, Maeda H (1988) Interdomain cleavage of plasma fibroblasts by zinc-metalloprotease from Serratia marcescens. Biochem Biophys Acta 955:77–85
Molla A, Yamamoto T, Akaike T, Miyoshi S, Maeda H (1989) Activation of Hageman factor and prekallikrein and generation of kinin by various microbial proteases. J Biol Chem 264:10589–10594
Mondino BT, Kessler E, Gipson LL, Brown ST (1976) Effects of zinc sulfate on Pseudomonas aeruginosa infection and protease in rabbit cornea. Arch Ophthalmol 1976:2149–2152
Morihara K, Homma JY (1985) Pseudomonas proteases. In: Holder IA (ed) Bacterial enzymes and virulence. CRC Press, Boca Raton, Florida, pp 41–79
Oda T, Kojima Y, Akaike T, Ijiri S, Molla A, Maeda H (1990) Inactivation of chemotactic activity of C5a by serratial 56-kilodalton protease. Infect Immun 58:1269–1272
Ofuji Y, Takeuchi Y, Yoshie H et al. (1988) The therapeutic effects of ovomacroglobulin (OMG) on the wound healing of gingiva in rats and collagenase activity in gingival crevicular fluid (GCF) of periodontal patients. In: Ishikawa J (ed) Recent advances in clinical periodontology. Elsevier, Amsterdam, pp 339–342
Ohman DE, Burns RP, Iglewski BH (1980) Corneal infections in mice with toxins A and elastase mutants of Pseudomonas aeruginosa. J Infect Dis 142:547–555
Ormerod LD, Smith RE (1986) Contact lens-associated microbial keratitis. Arch Ophthalmol 104:79–83
Ormerod LD, Gomez DS, Schanzlin DJ, Smith RE (1988) Chronic alcoholism and microbial keratitis. Br J Ophthalmol 72:155–159
Osada T, Sasaki T, Ikai A (1988) Purification and characterization of alpha-macroglobulin and ovomacroglobulin of the green turtle (Chelonia mydas japonica). J Biochem 103:212–217
Sbara AJ, Gilfillan RE, Bardawill WA (1960) A plate assay for elastase. Nature 188:322–323
Starkey PM (1979) Proteases in mammalian cells and tissues. Barratt AJ (ed) Elsevier, Amsterdam, pp 77–89
Steuhl KP, Döring G, Henni A, Thiel HJ, Botzebhart K (1987) Relevance of host-derived and bacterial factors in Pseudomonas corneal infection. Invest Ophthalmol Vis Sci 28:1559–1567
Turgeon PW, Stuart JC, Kowalski RP, Nauheim R, Stopak SS, Ritter MO (1989) Inhibition of proteolytic enzymes of Pseudomonas aeruginosa by aprotinin. Invest Ophthalmol Vis Sci [Suppl] 30:196
Uitto VJ, Larjava H, Heino J, Sorsa T (1989) A protease of Bacteroides gingivalis degrades cell surface and matrix glycoprotein of culture gingival fibroblasts and induces secretion of collagenase and plasminogen activator. Infect Immun 57:213–218
Weiss SJ (1989) Tissue destruction by neutrophil. N EngI J Med 320:365–375
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Miyagawa, Si., Kamata, R., Matsumoto, K. et al. Therapeutic intervention with chicken egg white ovomacroglobulin and a new quinolone on experimental Pseudomonas keratitis. Graefe's Arch Clin Exp Ophthalmol 232, 488–493 (1994). https://doi.org/10.1007/BF00195359
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00195359