Dystrophin deficiency promotes leukocyte recruitment in mdx mice
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...
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| Main Authors: | , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2019
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| In: |
Pediatric research
Year: 2019, Volume: 86, Issue: 2, Pages: 188-194 |
| ISSN: | 1530-0447 |
| DOI: | 10.1038/s41390-019-0427-3 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1038/s41390-019-0427-3 Verlag, Volltext: https://www.nature.com/articles/s41390-019-0427-3 
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| Author Notes: | Simon Alexander Kranig, Raphaela Tschada, Maylis Braun, Christian Patry, Johannes Pöschl, David Frommhold, Hannes Hudalla |
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| 520 | |a 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. | ||
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