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DNase aggravates intestinal microvascular injury in IBD patients by releasing NET-related proteins.
Shao, Yiming; Li, Linbin; Yang, Yunxi; Ye, Yulan; Guo, Zaiwen; Liu, Lu; Huang, Jiamin; Chen, Yi; Gao, Xi; Sun, Bingwei.
Afiliação
  • Shao Y; Department of Burns and Plastic Surgery, Affiliated Hospital of Jining Medical University, Jining, China.
  • Li L; Research Center for Neutrophil Engineering Technology, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China.
  • Yang Y; Research Center for Neutrophil Engineering Technology, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China.
  • Ye Y; Research Center for Neutrophil Engineering Technology, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China.
  • Guo Z; Department of Gastroenterology, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China.
  • Liu L; Research Center for Neutrophil Engineering Technology, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China.
  • Huang J; Research Center for Neutrophil Engineering Technology, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China.
  • Chen Y; Research Center for Neutrophil Engineering Technology, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China.
  • Gao X; Research Center for Neutrophil Engineering Technology, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China.
  • Sun B; Research Center for Neutrophil Engineering Technology, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China.
FASEB J ; 38(1): e23395, 2024 01.
Article em En | MEDLINE | ID: mdl-38149880
ABSTRACT
Neutrophils accumulate in the inflammatory mucosa of patients with inflammatory bowel disease (IBD), and excessive release of NETs (neutrophil extracellular traps may be one of the important factors that cause IBD progression. However, the specific mechanism underlying vascular injury caused by NETs remains unclear. Immunofluorescence, ELISA, and flow cytometry were used in this study to detect the expression of NETs and DNase in the tissue and peripheral blood samples of patients with IBD. DSS mouse model was used to detect colon injury and vascular permeability. We found that NETs and DNase levels increased in the colon of patients with IBD. We found an increase in the activity of NET-related MPO released by DNase. DNase released NET-related proteins and damaged vascular endothelial cells in vitro. In DSS mouse model, the synchronous increase of DNase and NETs in the colon leads to an increase in vascular injury markers (CD44, sTM). DNase aggravated colon injury and increased vascular permeability in vivo, which was inhibited by gentamicin sulfate (GS). GS does not reduce the expression of DNase, but rather reduces the release of NET-related proteins to protect vascular endothelium by inhibiting DNase activity. MPO and histones synergistically damaged the vascular endothelium, and vascular injury can be improved by their active inhibitors. We further found that H2 O2 is an important substrate for MPO induced vascular damage. In conclusion, in IBD, DNase, and NET levels increased synchronously in the lesion area and released NET-related proteins to damage the vascular endothelium. Therefore, targeting DNase may be beneficial for the treatment of IBD.
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Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Doenças Inflamatórias Intestinais / Lesões do Sistema Vascular / Armadilhas Extracelulares / Traumatismos Abdominais Limite: Animals / Humans Idioma: En Revista: FASEB J Assunto da revista: BIOLOGIA / FISIOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Doenças Inflamatórias Intestinais / Lesões do Sistema Vascular / Armadilhas Extracelulares / Traumatismos Abdominais Limite: Animals / Humans Idioma: En Revista: FASEB J Assunto da revista: BIOLOGIA / FISIOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China