Therapy with a Purified Plasminogen Concentrate in an Infant with Ligneous Conjunctivitis and Homozygous Plasminogen Deficiency

Schött, D; Dempfle, Carl-Erik; Beck, PL; Liermann, A; Mohr-Pennert, Anita; Goldner, M.; Mehlem, P; Azuma, Hiroyuki; Schuster, Volker; Mingers, A-M.; Schwarz, Hans; Kramer, Michael D.

doi:10.1056/nejm199812033392305

Cited by 145 publications

(137 citation statements)

References 39 publications

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“…66 Surgical removal of gingival masses, in combination with warfarin and antibiotic treatment, was successfully used in one of the ligneous gingivitis cases. 67 Our current data show that plasminogen supplementation in Plg-deficient mice can heal periodontitis, and previously reported data 68,69 on effective treatment of ligneous conjunctivitis with topical Plg strongly indicate that Plg treatment in ligneous gingivitis/periodontitis in humans could be a potential therapeutic application.…”

Section: Discussionsupporting

confidence: 62%

Plasmin Is Essential in Preventing Periodontitis in Mice

Sulniute

Lindh

Wilczyńska

et al. 2011

The American Journal of Pathology

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Periodontitis involves bacterial infection, inflammation of the periodontium, degradation of gum tissue, and alveolar bone resorption, which eventually leads to loss of teeth. To study the role of the broad-spectrum protease plasmin in periodontitis, we examined the oral health of plasminogen (Plg)-deficient mice. In wild-type mice, the periodontium was unaffected at all time points studied; in Plg-deficient mice, periodontitis progressed rapidly, within 20 weeks. Morphological study results of Plg-deficient mice revealed detachment of gingival tissue, resorption of the cementum layer, formation of necrotic tissue, and severe alveolar bone degradation. IHC staining showed massive infiltration of neutrophils in the periodontal tissues. Interestingly, doubly deficient mice, lacking both tissue-and urokinase-type plasminogen activators, developed periodontal disease similar to that in Plg-deficient mice; however, mice lacking only tissueor urokinase-type plasminogen activator remained healthy. Supplementation by injection of Plg-deficient mice with human plasminogen for 10 days led to necrotic tissue absorption, inflammation subsidence, and full regeneration of gum tissues. Notably, there was also partial regrowth of degraded alveolar bone. Taken together, our results show that plasminogen is essential for the maintenance of a healthy periodontium and plays an important role in combating the spontaneous development of chronic periodontitis. Moreover, reversal to healthy status after supplementation of Plg-deficient mice with plasminogen suggests the possibility of using plasminogen for therapy of periodontal diseases.

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Section: Discussionsupporting

confidence: 62%

Plasmin Is Essential in Preventing Periodontitis in Mice

Sulniute

Lindh

Wilczyńska

et al. 2011

The American Journal of Pathology

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“…In recent years, the murine model has been used extensively to study both physiological and pathological processes associated with plasminogen deficiency. Pathobiological conditions associated with plasminogen deficiency that are observed in both plasminogen Ϫ/Ϫ mice and homozygous plasminogen-deficient humans include thrombotic disease (24 -26) and ligneous conjunctivitis (27)(28)(29).…”

mentioning

confidence: 99%

Localization of Regulatory Elements Mediating Constitutive and Cytokine-stimulated Plasminogen Gene Expression

Bannach

Gutiérrez

Fowler

et al. 2002

Journal of Biological Chemistry

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The activity of plasmin, the major enzyme responsible for dissolving fibrin clots, is regulated by plasminogen activators, plasminogen activator inhibitors, ␣ 2 -antiplasmin, and inflammatory mediators. Recent studies suggest that plasmin activity can be regulated also at the level of plasminogen gene expression. In this study, we characterized the murine plasminogen promoter and 5-flanking region. The major transcription start site was identified at ؊83 bp relative to the ATG translational initiation codon. A series of 5-flanking sequences up to 2400 bp upstream of the transcription initiation site were fused to the luciferase reporter gene and transfected into hepatocytic cells. A 106-bp 5-flanking region of the murine plasminogen gene demonstrated sufficient functional promoter activity in plasminogenexpressing cells. IL-6 treatment stimulated luciferase activity driven by the 5-flanking region and an intact consensus IL-6-responsive element at ؊791, was required for maximal stimulation by this cytokine. These results indicate the presence of regulatory elements in the 5-flanking region of the murine plasminogen promoter that may regulate murine plasminogen gene expression and, hence, plasmin activity.

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“…8 The fibrin deposits impair the tracheobronchial tree ciliary system and this predisposes the patient to significant infections in the sinuses, middle ear and tracheobronchial tree. 9 In a report of Tefs et al, %30 percent of 50 patients with LG had respiratory tract involvement. 6 Plasminogen has been found as an important regulator in the pathogenesis of murine model of asthma.…”

Section: Discussionmentioning

confidence: 96%