Skip to main content
Top
Published in: Graefe's Archive for Clinical and Experimental Ophthalmology 5/2009

01-05-2009 | Inflammatory Disorders

Tear fluid concentration of mmp–8 is elevated in non—allergic eosinophilic conjunctivitis and correlates with conjunctival inflammatory cell infiltration

Authors: Osmo Kari, Marko Määttä, Taina Tervahartiala, Sirje Peltonen, Marjatta Kari, Jaana Hagström, Timo Sorsa, Matti Saari, Tari Haahtela

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 5/2009

Login to get access

Abstract

Background

To investigate tear fluid concentration of matrix metalloproteinase 8 (MMP–8) and its relation to conjunctival inflammatory cell infiltration in persistent non—allergic eosinophilic conjunctivitis (NAEC).

Methods

Two groups were included: 26 consecutive adult patients with NAEC (conjunctival eosinophils at least 1+ [1-10 eosinophils/slide], skin prick test [SPT] to common allergens negative), and 26 asymptomatic adult persons (no conjunctival eosinophils, SPT negative). MMP–8 tear fluid concentrations were determined by immunofluorometric assay, and conjunctival brush cytology samples from NAEC patients were used for MMP–8 immunocytochemistry. Gelatin zymography was used to illustrate proteolytic activity within the tear fluid samples.

Results

The mean MMP–8 concentration was significantly higher among NAEC patients (214.3 ± 327.7 μg/l) than among healthy persons (50.4 ± 62.3 μg/l, P < 0.0001). In the NAEC patients, tear fluid MMP–8 correlated with the numbers of conjunctival neutrophils (r = 0.66, P = 0.0002) as well as with goblet cells and columnar epithelial cells (r = 0.54 for both, P = 0.045), but not with the lymphocyte numbers (r = -0.36, P = 0.0741). By immunocytology, MMP–8 protein could also be detected in vivo in the inflammatory cell population within the conjunctiva. Zymography revealed that proteolysis was significantly higher in the NAEC group, and activated enzymes were practically found only in the NAEC group.

Conclusions

The results showed that NAEC is an inflammatory condition characterized by increased tear fluid MMP–8 levels, probably derived from both inflammatory and structural conjunctival cells. The increased proteolytic activity in NAEC patients may indicate risk of conjunctival structural changes (remodeling).
Literature
2.
go back to reference Kari O, Haahtela T (1992) Conjunctival eosinophilia in atopic and non—atopic external eye symptoms. Acta Ophthalmol Scand 70:335–340 Kari O, Haahtela T (1992) Conjunctival eosinophilia in atopic and non—atopic external eye symptoms. Acta Ophthalmol Scand 70:335–340
3.
go back to reference Kari O (1988) Atopic conjunctivitis. A cytologic examination. Acta Ophthalmol Scand 66:381–386 Kari O (1988) Atopic conjunctivitis. A cytologic examination. Acta Ophthalmol Scand 66:381–386
6.
go back to reference Goetzl EJ, Banda MJ, Leppert D (1996) Matrix metalloproteinases in immunity. J Immunol 156:1–4PubMed Goetzl EJ, Banda MJ, Leppert D (1996) Matrix metalloproteinases in immunity. J Immunol 156:1–4PubMed
7.
go back to reference Schönbeck U, Mach F, Libby P (1998) Generation of biologically active IL–1 beta by matrix metalloproteinases: a novel caspase–1-independent pathway of IL–1 beta processing. J Immunol 161:3340–3346PubMed Schönbeck U, Mach F, Libby P (1998) Generation of biologically active IL–1 beta by matrix metalloproteinases: a novel caspase–1-independent pathway of IL–1 beta processing. J Immunol 161:3340–3346PubMed
8.
9.
go back to reference Makowski GS, Ramsby ML (2003) Zymographic analysis of latent and activated forms of matrix metalloproteinase–2 and –9 in synovial fluid: correlation to polymorphonuclear leukocyte infiltration and in response to infection. Clin Chim Acta 329:77–81, doi:10.1016/S0009-8981(03)00015-9 PubMedCrossRef Makowski GS, Ramsby ML (2003) Zymographic analysis of latent and activated forms of matrix metalloproteinase–2 and –9 in synovial fluid: correlation to polymorphonuclear leukocyte infiltration and in response to infection. Clin Chim Acta 329:77–81, doi:10.​1016/​S0009-8981(03)00015-9 PubMedCrossRef
11.
go back to reference Okada S, Kita H, George TJ, Gleich GJ, Leiferman KM (1997) Migration of eosinophils through basement membrane components in vitro: role of matrix metalloproteinase–9. Am J Respir Cell Mol Biol 17:519–528PubMed Okada S, Kita H, George TJ, Gleich GJ, Leiferman KM (1997) Migration of eosinophils through basement membrane components in vitro: role of matrix metalloproteinase–9. Am J Respir Cell Mol Biol 17:519–528PubMed
12.
go back to reference Weiss SJ (1989) Tissue destruction by neutrophils. N Engl J Med 320:365–376PubMed Weiss SJ (1989) Tissue destruction by neutrophils. N Engl J Med 320:365–376PubMed
13.
go back to reference Matsuki H, Fujimoto N, Iwata K, Knäuper V, Okada Y, Hayakawa Y (1996) A one—step sandwich enzyme immunoassay for human matrix metalloproteinase 8 (neutrophil collagenase) using monoclonal antibodies. Clin Chim Acta 244:129–143, doi:10.1016/0009-8981(95)06197-5 PubMedCrossRef Matsuki H, Fujimoto N, Iwata K, Knäuper V, Okada Y, Hayakawa Y (1996) A one—step sandwich enzyme immunoassay for human matrix metalloproteinase 8 (neutrophil collagenase) using monoclonal antibodies. Clin Chim Acta 244:129–143, doi:10.​1016/​0009-8981(95)06197-5 PubMedCrossRef
14.
go back to reference Prikk K, Maisi P, Pirilä E, Reintam MA, Salo T, Sorsa T, Sepper R (2002) Airway obstruction correlates with collagenase–2 (MMP-8) expression and activation in bronchial asthma. Lab Invest 82:1535–1545PubMed Prikk K, Maisi P, Pirilä E, Reintam MA, Salo T, Sorsa T, Sepper R (2002) Airway obstruction correlates with collagenase–2 (MMP-8) expression and activation in bronchial asthma. Lab Invest 82:1535–1545PubMed
15.
go back to reference Kiili M, Cox SW, Chen HY, Whalgren J, Maisi P, Eley BM, Salo T, Sorsa T (2002) Collagenase–2 (MMP-8) and collagenase–3 (MMP–13) in adult periodontitis: molecular forms and levels in gingival crevicular fluid and immunolocalisation in gingival tissue. J Clin Periodontol 29:224–232, doi:10.1034/j.1600-051x.2002.290308.x PubMedCrossRef Kiili M, Cox SW, Chen HY, Whalgren J, Maisi P, Eley BM, Salo T, Sorsa T (2002) Collagenase–2 (MMP-8) and collagenase–3 (MMP–13) in adult periodontitis: molecular forms and levels in gingival crevicular fluid and immunolocalisation in gingival tissue. J Clin Periodontol 29:224–232, doi:10.​1034/​j.​1600-051x.​2002.​290308.​x PubMedCrossRef
17.
go back to reference Leonardi A, Brun P, Abatangelo G, Plebani M, Secchi AG (2003) Tear levels and activity of matrix metalloproteinase (MMP)–1 and MMP–9 in vernal keratoconjunctivitis. Invest Ophthalmol Vis Sci 44:3052–3058, doi:10.1167/iovs.02-0766 PubMedCrossRef Leonardi A, Brun P, Abatangelo G, Plebani M, Secchi AG (2003) Tear levels and activity of matrix metalloproteinase (MMP)–1 and MMP–9 in vernal keratoconjunctivitis. Invest Ophthalmol Vis Sci 44:3052–3058, doi:10.​1167/​iovs.​02-0766 PubMedCrossRef
18.
go back to reference Määttä M, Kari O, Tervahartiala T, Peltonen S, Kari M, Saari M, Sorsa T (2006) Tear fluid levels of MMP–8 are elevated in ocular rosacea — Treatment effect of oral doxycycline. Graefes Arch Clin Exp Ophthalmol 244:957–962, doi:10.1007/s00417-005-0212-3 PubMedCrossRef Määttä M, Kari O, Tervahartiala T, Peltonen S, Kari M, Saari M, Sorsa T (2006) Tear fluid levels of MMP–8 are elevated in ocular rosacea — Treatment effect of oral doxycycline. Graefes Arch Clin Exp Ophthalmol 244:957–962, doi:10.​1007/​s00417-005-0212-3 PubMedCrossRef
20.
go back to reference Hanemaaijer R, Sorsa T, Konttinen YT, Ding Y, Sutinen M, Visser H, van Hinsbergh VW, Helaakoski T, Kainulainen T, Rönkä H, Tschesche H, Salo T (1997) Matrix metalloproteinase—8 is expressed in rheumatoid synovial fibroblasts and endothelial cells. Regulation by tumour necrosis factor-alpha and doxycycline. J Biol Chem 272:31504–31509, doi:10.1074/jbc.272.50.31504 PubMedCrossRef Hanemaaijer R, Sorsa T, Konttinen YT, Ding Y, Sutinen M, Visser H, van Hinsbergh VW, Helaakoski T, Kainulainen T, Rönkä H, Tschesche H, Salo T (1997) Matrix metalloproteinase—8 is expressed in rheumatoid synovial fibroblasts and endothelial cells. Regulation by tumour necrosis factor-alpha and doxycycline. J Biol Chem 272:31504–31509, doi:10.​1074/​jbc.​272.​50.​31504 PubMedCrossRef
22.
go back to reference Sorsa T, Ding Y, Salo T, Lauhio A, Teronen O, Ingman T, Ohtani H, Andoh N, Takeha S, Konttinen YT (1994) Effects of tetracyclines on neutrophil, gingival, and salivary collagenases. A functional and western—blot assessment with special reference to their cellular sources in periodontal diseases. Ann N Y Acad Sci 732:112–131, doi:10.1111/j.1749-6632.1994.tb24729.x PubMedCrossRef Sorsa T, Ding Y, Salo T, Lauhio A, Teronen O, Ingman T, Ohtani H, Andoh N, Takeha S, Konttinen YT (1994) Effects of tetracyclines on neutrophil, gingival, and salivary collagenases. A functional and western—blot assessment with special reference to their cellular sources in periodontal diseases. Ann N Y Acad Sci 732:112–131, doi:10.​1111/​j.​1749-6632.​1994.​tb24729.​x PubMedCrossRef
24.
go back to reference Määttä M, Kari O, Tervahartiala T, Wahlgren J, Peltonen S, Kari M, Saari M, Sorsa T (2008) Elevated expression and activation of MMP–8 in tear fluid in atopic blepharoconjunctivitis. Cornea 27:297–301PubMedCrossRef Määttä M, Kari O, Tervahartiala T, Wahlgren J, Peltonen S, Kari M, Saari M, Sorsa T (2008) Elevated expression and activation of MMP–8 in tear fluid in atopic blepharoconjunctivitis. Cornea 27:297–301PubMedCrossRef
25.
go back to reference Corrales RM, Stern ME, De Palva CS, Welch J, Li DQ, Pflugdelder SC (2006) Desiccating stress stimulates expression of matrix metalloproteinases by the corneal epithelium. Invest Ophthalmol Vis Sci 47:3293–3302, doi:10.1167/iovs.05-1382 PubMedCrossRef Corrales RM, Stern ME, De Palva CS, Welch J, Li DQ, Pflugdelder SC (2006) Desiccating stress stimulates expression of matrix metalloproteinases by the corneal epithelium. Invest Ophthalmol Vis Sci 47:3293–3302, doi:10.​1167/​iovs.​05-1382 PubMedCrossRef
27.
go back to reference Migita K, Maeda Y, Abiru S, Nakamura M, Komori A, Yokoyama T, Takii Y, Mori Tm Yatsuhashi H, Eguchi K, Ishibashi H (2006) Immunosuppressant FK506 inhibits matrixmetalloproteinase–9 induction in TNF—alpha—stimulated human hepatic stellate cells. Life Sci 78:2510–2515, doi:10.1016/j.lfs.2005.10.003 PubMedCrossRef Migita K, Maeda Y, Abiru S, Nakamura M, Komori A, Yokoyama T, Takii Y, Mori Tm Yatsuhashi H, Eguchi K, Ishibashi H (2006) Immunosuppressant FK506 inhibits matrixmetalloproteinase–9 induction in TNF—alpha—stimulated human hepatic stellate cells. Life Sci 78:2510–2515, doi:10.​1016/​j.​lfs.​2005.​10.​003 PubMedCrossRef
Metadata
Title
Tear fluid concentration of mmp–8 is elevated in non—allergic eosinophilic conjunctivitis and correlates with conjunctival inflammatory cell infiltration
Authors
Osmo Kari
Marko Määttä
Taina Tervahartiala
Sirje Peltonen
Marjatta Kari
Jaana Hagström
Timo Sorsa
Matti Saari
Tari Haahtela
Publication date
01-05-2009
Publisher
Springer-Verlag
Published in
Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 5/2009
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI
https://doi.org/10.1007/s00417-009-1042-5

Other articles of this Issue 5/2009

Graefe's Archive for Clinical and Experimental Ophthalmology 5/2009 Go to the issue