Identification and Characterization of Middle Ear Vascular Leakage Sites in Experimental Otitis Media

Goldie, Pamela; Hellström, Sten

doi:10.1177/000348949009901011

Cited by 11 publications

(5 citation statements)

References 19 publications

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“…Morphological studies have also noted the presence of lymphatics in the ME based (Lim and Hussl, 1975), and drainage from the ME to lymph nodes of the neck has been demonstrated (Galich, 1973;Lim and Hussl, 1975), validating lymphatic endothelial cells of Cluster 9 cells. The documentation of capillaries and post-capillary venules in the ME (e.g., Goldie and Hellström, 1990) makes the observation of pericytes in Cluster 13 unremarkable. Gene expression related to hypoxia, contractility and water permeability are consistent with pericyte regulation of vascular tone, based on oxygen tension, and fluid entry into the ME.…”

Section: Vascular Cellsmentioning

confidence: 99%

Single-Cell Transcriptomes Reveal a Complex Cellular Landscape in the Middle Ear and Differential Capacities for Acute Response to Infection

et al. 2020

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Single-cell transcriptomics was used to profile cells of the normal murine middle ear. Clustering analysis of 6770 transcriptomes identified 17 cell clusters corresponding to distinct cell types: five epithelial, three stromal, three lymphocyte, two monocyte, two endothelial, one pericyte and one melanocyte cluster. Within some clusters, cell subtypes were identified. While many corresponded to those cell types known from prior studies, several novel types or subtypes were noted. The results indicate unexpected cellular diversity within the resting middle ear mucosa. The resolution of uncomplicated, acute, otitis media is too rapid for cognate immunity to play a major role. Thus innate immunity is likely responsible for normal recovery from middle ear infection. The need for rapid response to pathogens suggests that innate immune genes may be constitutively expressed by middle ear cells. We therefore assessed expression of innate immune genes across all cell types, to evaluate potential for rapid responses to middle ear infection. Resident monocytes/macrophages expressed the most such genes, including pathogen receptors, cytokines, chemokines and chemokine receptors. Other cell types displayed distinct innate immune gene profiles. Epithelial cells preferentially expressed pathogen receptors, bactericidal peptides and mucins. Stromal and endothelial cells expressed pathogen receptors. Pericytes expressed pro-inflammatory cytokines. Lymphocytes expressed chemokine receptors and antimicrobials. The results suggest that tissue monocytes, including macrophages, are the master regulators of the immediate middle ear response to infection, but that virtually all cell types act in concert to mount a defense against pathogens.

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Section: Vascular Cellsmentioning

confidence: 99%

Single-Cell Transcriptomes Reveal a Complex Cellular Landscape in the Middle Ear and Differential Capacities for Acute Response to Infection

et al. 2020

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“…The pars tensa is the connective tissue layerofthe auditorycanal of the TM. Them ajority of the transparent portion of the pars tensa is devoid of blood vessels (9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

“…NumberofapparentlyclosedTMs in relation to the totalnumberofTMs examined. At eachexamination time point(4,8,11,16,36, 50, 72 and 143 days), TMs from both earsof9,9,9,7,5,5,5and 5wtmice and 5, 5, 8, 8, 8, 13, 13 and 8plg-deficient mice were analyzed. **Inplg-deficient mice all of theappar-entlyclosedTMs were either coveredbycrusts or hadanopaque and thick appearance.…”

mentioning

confidence: 99%

Plasmin/plasminogen is essential for the healing of tympanic membrane perforations

Li¹,

Eriksson²,

Hansson³

et al. 2006

Thromb Haemost

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SummaryPlasminogen has been proposed to play an important role in different tissue remodeling processes such as wound healing and tissue regeneration after injuries. The healing of tympanic membrane perforations is a well-organized chain of inflammatory events, with an initial invasion of inflammatory cells followed by reparative and restoration phases. Here we show that the healing of tympanic membrane perforations is completely arrested in plasminogen-deficient mice, with no signs of any healing even 143 days after perforation. Inflammatory cells were recruited to the wounded area, but there were no signs of tissue debridement. In addition, removal of fibrin, keratinocyte migration and in-growth of connective tissue were impaired. This contrasts with skin wound healing, where studies have shown that, although the healing process is delayed, it reaches completion in all plasminogen-deficient mice. Our finding that keratinocyte migration and re-epithelialization were completely arrested in plasminogen-deficient mice indicates that plasminogen/plasmin plays a more profound role in the healing of tympanic membrane perforations than in the healing of other epithelial wounds.

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“…Middle ear effusions observed in the control group animals have also been demonstrated by other investigators and it has been suggested that this is because of an increased permeability in various regions of the middle ear. The major route for increasing vessel permeability is the opening of interendothelial junctions (Hellstrom et al, 1982;Udmann et al, 1985;Widemar et al, 1985;Goldie et al, 1989;Goldie and Hellstrom, 1990). It has been reported that vasoactive neuropeptides and particularly substance P, allow gaps the transport of fluid into the middle ear cavity by forming of interendothelial gaps (Hellstrom et al, 1982 Hellstrom, 1988;Goldie and Hellstrom, 1990).…”

Section: Discussionmentioning

confidence: 99%

“…The major route for increasing vessel permeability is the opening of interendothelial junctions (Hellstrom et al, 1982;Udmann et al, 1985;Widemar et al, 1985;Goldie et al, 1989;Goldie and Hellstrom, 1990). It has been reported that vasoactive neuropeptides and particularly substance P, allow gaps the transport of fluid into the middle ear cavity by forming of interendothelial gaps (Hellstrom et al, 1982 Hellstrom, 1988;Goldie and Hellstrom, 1990). In the present study no significant difference between the two groups in respect of vasodilatation was found whereas the presence of effusion in only one case of the group pre-treated with capsaicin supports the views of the authors suggesting that capsaicin can prevent the increase in vascular permeability by decreasing the opening of the interendothelial junctions (Hellstrom et al, 1982;Gyorfl et al, 1993;Norlander et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Effects of capsaicin pre-treatment in experimentally-induced secretory otitis media

et al. 1999

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Neurogenic inflammation may play a role in the aetiology of secretory otitis media (SOM). The strongest candidate that initiates the characteristic symptoms of neurogenic inflammation is supposed to be substance P. Capsaicin is a specific antagonist of substance P. The effects of capsaicin on middle ear mucosa have not been studied yet. In an attempt to investigate the effect of pre-treatment with capsaicin on the development of SOM an experimental study was performed. Fourteen Wistar rats were divided into two groups. Seven rats were pre-treated with capsaicin (Group 1) and the others were administered isotonic saline solution (Group 2). Seven days after the third injection rats were operated on and the right tympanal orifice of the Eustachian tube was obstructed. Animals were sacrificed seven days after the operation. Their bullas were excised bilaterally and were studied by light microscopic technique. In Group 1 there was no effusion except for one case. The subepithelial layer was thickened by fibroblast proliferation. Capillary proliferation and some glandular atrophy were observed. In Group 2 the middle ear lumens were filled with effusion. Oedema with dilatation in capillaries and medium-sized vessels of lamina propria was observed as a common feature of the group. Subepithelial fibrosis was found in one case. Capsaicin pre-treatment prevented the formation of effusion in the middle ear lumen in spite of tuba occlusion. The results of this preliminary study lead us to consider that an imbalance in the autonomic innervation of the mucosa of the middle ear may play a role in the aetiology of SOM as in vasomotor rhinitis, and capsaicin may be an alternative in the treatment.

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Identification and Characterization of Middle Ear Vascular Leakage Sites in Experimental Otitis Media

Cited by 11 publications

References 19 publications

Single-Cell Transcriptomes Reveal a Complex Cellular Landscape in the Middle Ear and Differential Capacities for Acute Response to Infection

Single-Cell Transcriptomes Reveal a Complex Cellular Landscape in the Middle Ear and Differential Capacities for Acute Response to Infection

Plasmin/plasminogen is essential for the healing of tympanic membrane perforations

Effects of capsaicin pre-treatment in experimentally-induced secretory otitis media

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