Staphylococcus aureus impairs sinonasal epithelial repair: Effects in patients with chronic rhinosinusitis with nasal polyps and control subjects - 07/02/19
Abstract |
Background |
The effect of Staphylococcus aureus on nasal epithelial repair has never been assessed in patients with chronic rhinosinusitis with nasal polyps (CRSwNP).
Objective |
This study aimed to determine whether (1) nasal epithelial cell cultures from patients with CRSwNP and control subjects repair differently; (2) S aureus exoproducts compromise nasal epithelial repair; (3) S aureus alters lamellipodial dynamics; and (4) deleterious effects could be counteracted by the Rho-associated coiled-coil kinase inhibitor Y-27632.
Methods |
Primary nasal epithelial cells (pNECs) collected during surgeries were cultured and injured under 3 conditions: (1) basal conditions, (2) exposed to S aureus exoproducts, and (3) exposed to S aureus exoproducts and Y-27632. Epithelial repair, lamellipodial dynamics, and cytoskeletal organization were assessed.
Results |
Under basal conditions, pNEC cultures from patients with CRSwNP presented significantly lower repair rates and reduced lamellipodial protrusion length and velocity than those from control subjects. S aureus exoproducts significantly decreased repair rates and protrusion dynamics in both control subjects and patients with CRSwNP; however, the effect of S aureus on cell protrusions was more sustained over time in patients with CRSwNP. Under basal conditions, immunofluorescence assays showed significantly reduced percentages of cells with lamellipodia at the wound edge in patients with CRSwNP compared with control subjects. S aureus altered cell polarity and decreased the percentage of cells with lamellipodia in both groups. Finally, Y-27632 prevented the deleterious effects of S aureus exoproducts on CRSwNP repair rates, as well as on lamellipodial dynamics and formation.
Conclusions |
S aureus exoproducts significantly alter epithelial repair and lamellipodial dynamics on pNECs, and this impairment was more pronounced in patients with CRSwNP. Importantly, Y-27632 restored epithelial repair and lamellipodial dynamics in the presence of S aureus exoproducts.
Il testo completo di questo articolo è disponibile in PDF.Graphical abstract |
Key Words : Staphylococcus aureus, chronic rhinosinusitis, repair, nasal epithelial cells, lamellipodia, Rho-associated coiled-coil kinase inhibitor, Y-27632
Abbreviations used : CRS, CRSwNP, ESS, LB, pNEC, ROCK, SAinactive
Mappa
| Supported by FAPESP, São Paulo Research Foundation. Brazil (grant no. 2016/00772-1- Scholarship to F.C.V.). The Respiratory Health Network of Québec supported our Respiratory Tissue and Cell Biobank of CRCHUM. This work was supported by the Canadian Institutes of Health Research (CIHR, grant PJT148593 to E.B.), les Fonds de Recherche du Québec en Santé (fellowships to M.R. and D.A.), and CRCHUM and Université de Montréal (scholarship to E.B.). |
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| Disclosure of potential conflict of interest: F. C. P. Valera has received support from FAPESP, São Paulo Research Foundation, Brazil (grant no. 2016/00772-1). M. Ruffin has received support from les Fonds de Recherche du Québec en Santé (fellowship). D. Adam has received support from les Fonds de Recherche du Québec en Santé (fellowship). É. Maillé has received support from the Respiratory Health Network of Québec for the support of our Respiratory Tissue and Cell Biobank of CRCHUM J. Berube has received support from the Canadian Institutes of Health Research (MOP#123496). S. Rousseau has received support from the Canadian Institutes of Health Research (MOP#123496). E. Brochiero has received support from the Respiratory Health Network of Québec for the support of our Respiratory Tissue and Cell Biobank of CRCHUM, the Canadian Institutes of Health Research (CIHR, grant PJT148593), CRCHUM, and Université de Montréal (scholarship). M. Y. Desrosiers is a member of on an advisory panel at LaurieMed (PolypVac) and is President of ProBionase Therapies. B. Ibrahim declares no relevant conflicts of interest. |
Vol 143 - N° 2
P. 591 - febbraio 2019 Ritorno al numero
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