RESUMO
BACKGROUND: Dysregulated airway epithelial repair following injury is a proposed mechanism driving posttransplant bronchiolitis obliterans (BO), and its clinical correlate bronchiolitis obliterans syndrome (BOS). This study compared gene and cellular characteristics of injury and repair in large (LAEC) and small (SAEC) airway epithelial cells of transplant patients. METHODS: Subjects were recruited at the time of routine bronchoscopy posttransplantation and included patients with and without BOS. Airway epithelial cells were obtained from bronchial and bronchiolar brushing performed under radiological guidance from these patients. In addition, bronchial brushings were also obtained from healthy control subjects comprising of adolescents admitted for elective surgery for nonrespiratory-related conditions. Primary cultures were established, monolayers wounded, and repair assessed (±) azithromycin (1 µg/mL). In addition, proliferative capacity as well as markers of injury and dysregulated repair were also assessed. RESULTS: SAEC had a significantly dysregulated repair process postinjury, despite having a higher proliferative capacity than large airway epithelial cells. Addition of azithromycin significantly induced repair in these cells; however, full restitution was not achieved. Expression of several genes associated with epithelial barrier repair (matrix metalloproteinase 7, matrix metalloproteinase 3, the integrins ß6 and ß8, and ß-catenin) were significantly different in epithelial cells obtained from patients with BOS compared to transplant patients without BOS and controls, suggesting an intrinsic defect. CONCLUSIONS: Chronic airway injury and dysregulated repair programs are evident in airway epithelium obtained from patients with BOS, particularly with SAEC. We also show that azithromycin partially mitigates this pathology.
Assuntos
Azitromicina/farmacologia , Bronquiolite Obliterante/prevenção & controle , Células Epiteliais/efeitos dos fármacos , Rejeição de Enxerto/prevenção & controle , Transplante de Pulmão/efeitos adversos , Adolescente , Adulto , Remodelação das Vias Aéreas/efeitos dos fármacos , Aloenxertos/citologia , Aloenxertos/diagnóstico por imagem , Aloenxertos/patologia , Azitromicina/uso terapêutico , Brônquios/citologia , Brônquios/diagnóstico por imagem , Brônquios/patologia , Bronquiolite Obliterante/diagnóstico , Bronquiolite Obliterante/etiologia , Bronquiolite Obliterante/patologia , Broncoscopia , Estudos de Casos e Controles , Células Cultivadas , Criança , Avaliação Pré-Clínica de Medicamentos , Células Epiteliais/patologia , Feminino , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Cultura Primária de Células , Regeneração/efeitos dos fármacos , Transplante Homólogo , Adulto JovemRESUMO
The purpose of this study was to radiographically analyze the effect of autologous platelet rich plasma (PRP) on the healing of fresh frozen bone allograft (FFBA) placed in surgically created resection defects in mandibles of dogs. Bilateral resection defects measuring 1.5 cm × 1 cm were surgically created on the inferior border of the mandible in 10 adult male dogs. The defects were randomly divided into three groups: C, FFBA, and FFBA/PRP. In Group C, the defect was filled by blood clot only. In Group FFBA, the defect was filled with particulate fresh frozen bone allograft. In Group FFBA/PRP, it was filled with particulate fresh frozen bone allograft combined with PRP. At 90 days postoperative, standardized radiographs of the mandibles were obtained and results were quantitatively evaluated. Analysis of digitized radiographs indicated that non-PRP grafts were significantly less dense than the PRP grafts. Group FFBA/PRP also presented a statistically greater mineralized tissue area than Groups C and FFBA. Within the limits of this study, it can be concluded that PRP enhanced the healing of FFBA in resection defects in mandibles of dogs.