Lack of plasminogen does not alter the early inflammatory response following a tympanic membrane perforation: a study in plasminogen-deficient mice

Prestwich, Annika Hansson; Li, Jinan; Eriksson, Per; Ny, Tor; Berggren, Diana; Hellström, Sten

doi:10.1080/00016480701361996

Cited by 11 publications

(5 citation statements)

References 17 publications

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“…Our studies of plg −/− mice have indicated that the early inflammatory cell recruitment during healing of TM perforations is not affected [16]. However, the resolution of inflammation is impaired in these mice and the neutrophils are persistently present at the wound site [9].…”

Section: Resultsmentioning

confidence: 84%

Mice Deficient in Urokinase-Type Plasminogen Activator Have Delayed Healing of Tympanic Membrane Perforations

Shen

Guo

et al. 2012

PLoS ONE

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Mice deficient in plasminogen, the precursor of plasmin, show completely arrested healing of tympanic membrane (TM) perforations, indicating that plasmin plays an essential role in TM healing. The activation of plasminogen to plasmin is performed by two plasminogen activators (PAs), urokinase-type PA (uPA) and tissue-type PA (tPA). To elucidate the functional roles of PAs in the healing of TM perforations, we investigated the phenotypes of single gene-deficient mice lacking uPA (uPA−/−) or tPA (tPA−/−) after TM perforation. Delayed healing of TM perforations was observed in uPA−/− mice but not tPA−/− mice. The migration of keratinocytes was clearly delayed and seemed to be misoriented in uPA−/− mice. Furthermore, fibrin deposition and the inflammatory response were persistent in these mice. Our findings demonstrate that uPA plays a role in the healing of TM perforations. The observed phenotypes in uPA−/− mice are most likely due to the reduced generation of plasmin.

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Section: Resultsmentioning

confidence: 84%

Mice Deficient in Urokinase-Type Plasminogen Activator Have Delayed Healing of Tympanic Membrane Perforations

Shen

Guo

et al. 2012

PLoS ONE

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“…The similar studies concerning TM healing showed that in plasminogen-deficient mice, healing was completely arrested [ 20 , 22 ]. In these animals, the recruitment of the inflammatory cells to the wound area was similar, but tissue debridement, removal of fibrin, resolution of inflammatory reaction, keratinocyte migration, and in-growth of connective tissue were impaired.…”

Section: Discussionmentioning

confidence: 93%

“…1 B. It has been shown that in plasminogen-deficient mice, skin wound healing is delayed and disturbed, but apparently it is completed, while TM healing is arrested completely [ 15 , 20 – 22 ]. Delayed healing of TM perforations was also observed in urokinase-type plasminogen activator-deficient mice [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

Enhanced Expression of Plasminogen Activators and Inhibitor in the Healing of Tympanic Membrane Perforation in Rats

Makuszewska

Cieślińska

Winnicka

et al. 2023

JARO

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The significance of plasminogen activation during the tympanic membrane (TM) healing is known mainly from studies performed on knock-out mice. In the previous study, we reported activation of genes coding proteins of plasminogen activation and inhibition system in rat’s TM perforation healing. The aim of the present study was the evaluation of protein products expressed by these genes and their tissue distribution using Western blotting and immunofluorescent method, respectively, during 10-day observation period after injury. Otomicroscopical and histological evaluation were employed to assess the healing process. The expression of urokinase plasminogen activator (uPA) and its receptor (uPAR) were significantly upregulated in the proliferation phase, with subsequent gradual attenuation during remodeling phase of healing process, when keratinocyte migration was weakening. The expression of plasminogen activator inhibitor type 1 (PAI-1) also showed the highest levels during the proliferation phase. The increase of tissue plasminogen activator (tPA) expression was observed during the whole observation period, with the highest activity during the remodeling phase. Immunofluorescence of these proteins was present mainly in migrating epithelium. Our study found that plasminogen activation (uPA, uPAR, tPA) and inhibitory (PAI-1) molecules form a well-structured regulatory system of the epithelial migration that is critical to the healing of TM after its perforation.

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“…Ear bars with 18° or 45° points may be used. The 18° ear bars provide good head restraint but can cause internal ear hematoma and acute inflammation (Prestwich et al, 2008). We use the non-rupture wide angle 45° points that provide adequate head restraint and carry minimal risk of injury or inflammation.…”

Section: Methodsmentioning

confidence: 99%

Visualizing leukocyte trafficking in the living brain with 2-photon intravital microscopy

Pai¹,

Danne²,

Qin³

et al. 2013

Front. Cell. Neurosci.

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Intravital imaging of the superficial brain tissue in mice represents a powerful tool for the dissection of the cellular and molecular cues underlying inflammatory and infectious central nervous system (CNS) diseases. We present here a step-by-step protocol that will enable a non-specialist to set up a two-photon brain-imaging model. The protocol offers a two-part approach that is specifically optimized for imaging leukocytes but can be easily adapted to answer varied CNS-related biological questions. The protocol enables simultaneous visualization of fluorescently labeled immune cells, the pial microvasculature and extracellular structures such as collagen fibers at high spatial and temporal resolution. Intracranial structures are exposed through a cranial window, and physiologic conditions are maintained during extended imaging sessions via continuous superfusion of the brain surface with artificial cerebrospinal fluid (aCSF). Experiments typically require 1–2 h of preparation, which is followed by variable periods of immune cell tracking. Our methodology converges the experience of two laboratories over the past 10 years in diseased animal models such as cerebral ischemia, lupus, cerebral malaria, and toxoplasmosis. We exemplify the utility of this protocol by tracking leukocytes in transgenic mice in the pial vessels under steady-state conditions.

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Lack of plasminogen does not alter the early inflammatory response following a tympanic membrane perforation: a study in plasminogen-deficient mice

Cited by 11 publications

References 17 publications

Mice Deficient in Urokinase-Type Plasminogen Activator Have Delayed Healing of Tympanic Membrane Perforations

Mice Deficient in Urokinase-Type Plasminogen Activator Have Delayed Healing of Tympanic Membrane Perforations

Enhanced Expression of Plasminogen Activators and Inhibitor in the Healing of Tympanic Membrane Perforation in Rats

Visualizing leukocyte trafficking in the living brain with 2-photon intravital microscopy

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