Effective treatment of ligneous conjunctivitis with topical plasminogen

Watts, Patrick; Suresh, Palaniswamy; Mezer, Eedy; Ells, Anna L.; Albisetti, Manuela; Bajzar, Lazlo; Marzinotto, Velma; Andrew, Maureen; Massicotle, Patricia; Rootman, David

doi:10.1016/s0002-9394(01)01433-7

Cited by 80 publications

(72 citation statements)

References 27 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: 65%

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: 65%

Plasmin Is Essential in Preventing Periodontitis in Mice

Sulniute

Lindh

Wilczyńska

et al. 2011

The American Journal of Pathology

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“…[31][32][33] However, the capacity to dissolve deposited fibrin in a timely manner is equally essential to maintaining health as the capacity to convert fibrinogen to fibrin. This is well illustrated by the progressive inflammation-associated, fibrindependent multiorgan pathology and impaired tissue regenerative capacity that is observed in humans and mice deficient in the key fibrinolytic protease zymogen plasminogen 27,29,30,[34][35][36][37][38][39][40][41][42] and by studies in humans and animals showing that extravascular fibrin deposition exacerbates the morbidity of a wide range of chronic human diseases, including tissue fibrosis, muscular dystrophy, rheumatoid arthritis, and multiple sclerosis, in large part through its ability to cause persistent inflammation. [43][44][45][46][47][48][49] Previous studies have suggested important roles of uPAR in cell adhesion, cell migration, cell proliferation, cell differentiation, and cell survival (Smith and Marshall 2 ; Blasi and Carmeliet 3 ; supplemental .…”

Section: Discussionmentioning

confidence: 99%

Selective abrogation of the uPA-uPAR interaction in vivo reveals a novel role in suppression of fibrin-associated inflammation

Connolly

Choi

Gårdsvoll

et al. 2010

Blood

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The urokinase plasminogen activator receptor (uPAR) has emerged as a potential regulator of cell adhesion, cell migration, proliferation, differentiation, and cell survival in multiple physiologic and pathologic contexts. The urokinase plasminogen activator (uPA) was the first identified ligand for uPAR, but elucidation of the specific functions of the uPA-uPAR interaction in vivo has been difficult because uPA has important physiologic functions that are independent of binding to uPAR and because uPAR engages multiple ligands. Here, we developed a new mouse strain (Plau GFDhu/GFDhu ) in which the interaction between endogenous uPA and uPAR is selectively abrogated, whereas other functions of both the protease and its receptor are retained. Specifically, we introduced 4 amino acid substitutions into the growth factor domain (

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“…This difficult therapy was denied by the parents of our patient. Most recently, promising results were obtained by topical plasminogen concentrate in three children with ligneous conjunctivitis [29].…”

Section: Discussionmentioning

confidence: 99%