Dystrophin deficiency promotes leukocyte recruitment in mdx mice
| Autor: | David Frommhold, Simon Alexander Kranig, Maylis Braun, Raphaela Tschada, Christian Patry, Johannes Pöschl, Hannes Hudalla |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
musculoskeletal diseases Integrins Intravital Microscopy Neutrophils Duchenne muscular dystrophy Inflammation medicine.disease_cause Dystrophin Mice 03 medical and health sciences 0302 clinical medicine 030225 pediatrics Leukocytes medicine Animals Leukocyte Rolling Muscular dystrophy Muscle Skeletal Abdominal Muscles biology Tumor Necrosis Factor-alpha business.industry Immune dysregulation Flow Cytometry medicine.disease Mice Inbred C57BL Muscular Dystrophy Duchenne Disease Models Animal Pediatrics Perinatology and Child Health Immunology Cremaster muscle Mice Inbred mdx Scrotum biology.protein Cytokines Tumor necrosis factor alpha medicine.symptom business 030217 neurology & neurosurgery Intravital microscopy |
| Zdroj: | Pediatric Research. 86:188-194 |
| ISSN: | 1530-0447 0031-3998 |
| DOI: | 10.1038/s41390-019-0427-3 |
| Popis: | A growing body of evidence defines inflammation as a hallmark feature of disease pathogenesis of Duchenne muscular dystrophy. To tailor potential immune modulatory interventions, a better understanding of immune dysregulation in Duchenne muscular dystrophy is needed. We now asked whether dystrophin deficiency affects the cascade of leukocyte recruitment. We performed intravital microscopy on the cremaster muscle of wild-type and dystrophin-deficient mdx mice. Recruitment was triggered by preparation alone (traumatic inflammation) or in combination with scrotal TNFα injections. Neutrophilic infiltration of the cremaster muscle was assessed on tissue sections. Integrin expression on circulating neutrophils and serum levels of pro-inflammatory cytokines were measured by flow cytometry. Mdx mice show increased rolling and adhesion at baseline (traumatic inflammation) and a more profound response upon TNFα injection compared with wild-type animals. In both models, neutrophilic infiltration of the cremaster muscle is increased. Upregulation of the integrins LFA-1 and Mac-1 on circulating leukocytes and pro-inflammatory cytokines IL-6 and CCL2 in the serum points toward systemically altered immune regulation in mdx mice. We are the first to show exaggerated activation of the leukocyte recruitment cascade in a dystrophin-deficient organism in vivo. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink