Immunhistochemische Lokalisation von Matrixmetalloproteinasen (MMP) und ihrer Inhibitoren (tissue inhibitors of metalloproteinases, TIMP) bei tuberkulöser Pleuritis

Zusammenfassung

Matrixmetalloproteinasen (MMP) und ihre spezifischen Inhibitoren (tissue inhibitors of metalloproteinases, TIMP) wurden mittels ELISA und Gelatinezymographie in unterschiedlichen Konzentrationen in Pleuraflüssigkeit bei tuberkulöser (TB) Pleuritis nachgewiesen. Zur weiteren Differenzierung wurden MMP und TIMP durch immunhistochemische Färbungen in Pleurabioptaten mit Antikörpern gegen MMP-1, MMP-2, MMP-3, MMP-9, TIMP-1 und TIMP-2 mittels der Labelled-Avidin-Biotin (LAB)-Methode lokalisiert. Immunhistochemische Reaktivität für MMP-1 wurde in epitheloidzelligen Histiozyten, Langhans'schen Riesenzellen, Lymphozyten, Makrophagen, sowie in Fibroblasten granulomatöser Reaktionen nachgewiesen. MMP-2 fand sich in wenigen epitheloidzelligen Histiozyten, Fibroblasten und Entzündungszellen. MMP-3 färbte wenige Lymphozyten nur schwach. MMP-9 fand sich in wenigen Fibroblasten, Epitheloid- und Entzündungszellen, besonders jedoch in Pleuramesothelzellen. Nur wenige Fibroblasten zeigten eine Immunreaktivität für TIMP-1 und TIMP-2. Die beobachtete Inhomogenität der Anfärbung könnte durch den unterschiedlichen Aktivierungszustand einzelner Zellverbände erklärbar sein. Schlussfolgernd ist der immunhistochemische Nachweis von MMP und TIMP in pleuralen Zellen und Gewebestrukturen Hinweis für deren lokale Beteiligung an fibrosierenden Reaktionen bei TB-Pleuritis.

Abstract

Matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) have been found by ELISA and gelatine zymography in different concentrations in pleural fluid in tuberculous (TB) pleuritis. For further differentiation MMP and TIMP were localized in pleural biopsies by immunhistochemical staining with antibodies directed against MMP-1, MMP-2, MMP-3, MMP-9, TIMP-1, and TIMP-2 using the Labelled-Avidin-Biotin (LAB). Immunohistological reactivity of MMP-1 was found in epitheloidcellular histiocytes, Langhans' giant cells, lymphocytes, macrophages, as well as in fibroblasts of granulomatous reactions. MMP-2 was found in a few epitheloid cellular histiocytes, fibroblasts, and inflammatory cells. MMP-3 was weakly positive in a few lymphocytes only. MMP-9 was found in a few fibroblasts, epitheloid cells, and inflammatory cells, foremost, however, in pleural mesothial cells. A few fibroblasts only showed immunoreactivity of TIMP-1 and TIMP-2. The observed inhomogenous staining pattern could be explained by the different state of activation of individual cellular units. In conclusion, the immunohistochemical demonstration of MMP and TIMP in pleural cells and tissue structures indicates their local involvement in fibrosing reactions in TB-pleuritis.

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