Basic Science Article | Published:

Dystrophin deficiency promotes leukocyte recruitment in mdx mice

Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

We are the first to show exaggerated activation of the leukocyte recruitment cascade in a dystrophin-deficient organism in vivo.

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Acknowledgements

We are grateful to Britta Heckmann, Silvia Pezer, and Melitta Weissinger for excellent technical and experimental assistance. This study was supported by grants from the German Federal Ministry of Education and Research (BMBF) 01GL1746E as part of the PRIMAL Consortium and from the German Research Foundation (DFG) FR3068/4-1.

Author information

All authors have met the Pediatric Research authorship requirements. S.K. designed experiments, acquired, analyzed, and interpreted data and wrote the paper. R.T., M.B., C.P., and J.P. interpreted data and revised the paper. D.F. designed experiments, interpreted data, and revised the paper. H.H. designed experiments, interpreted data, and wrote the paper. All authors read and approved the final version to be published.

Competing interests

The authors declare that they have no competing interests.

Correspondence to Hannes Hudalla.

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