Diseased muscles that lack dystrophin or laminin-alpha2 have altered compositions and proliferation of mononuclear cell populations.

Abstract

BACKGROUND:

Multiple types of mononucleate cells reside among the multinucleate myofibers in skeletal muscles and these mononucleate cells function in muscle maintenance and repair. How neuromuscular disease might affect different types of muscle mononucleate cells had not been determined. In this study, therefore, we examined how two neuromuscular diseases, dystrophin-deficiency and laminin-alpha2-deficiency, altered the proliferation and composition of different subsets of muscle-derived mononucleate cells.

METHODS:

We used fluorescence-activated cell sorting combined with bromodeoxyuridine labeling to examine proliferation rates and compositions of mononuclear cells in diseased and healthy mouse skeletal muscle. We prepared mononucleate cells from muscles of mdx (dystrophin-deficient) or Lama2-/- (laminin-alpha2-deficient) mice and compared them to cells from healthy control muscles. We enumerated subsets of resident muscle cells based on Sca-1 and CD45 expression patterns and determined the proliferation of each cell subset in vivo by BrdU incorporation.

RESULTS:

We found that the proliferation and composition of the mononucleate cells in dystrophin-deficient and laminin-alpha2-deficient diseased muscles are different than in healthy muscle. The mdx and Lama2-/- muscles showed similar significant increases in CD45+ cells compared to healthy muscle. Changes in proliferation, however, differed between the two diseases with proliferation increased in mdx and decreased in Lama2-/- muscles compared to healthy muscles. In particular, the most abundant Sca-1-/CD45- subset, which contains muscle precursor cells, had increased proliferation in mdx muscle but decreased proliferation in Lama2-/- muscles.

CONCLUSION:

The similar increases in CD45+ cells, but opposite changes in proliferation of muscle precursor cells, may underlie aspects of the distinct pathologies in the two diseases.

• Authors: Mahasweta Girgenrath, Christine A Kostek, Jeffrey Boone Miller
• Journal: BMC neurology (BMC Neurol) Vol. 5 Issue 1 Pg. 7 (Apr 07 2005) ISSN: 1471-2377 [Electronic] England
• PMID: 15817132 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antigens, Ly
• Dystrophin
• Laminin
• Ly6a protein, mouse
• Membrane Proteins
• laminin alpha 2
• Leukocyte Common Antigens
• Bromodeoxyuridine

Topics

• Age Factors
• Analysis of Variance
• Animals
• Antigens, Ly (metabolism)
• Bromodeoxyuridine
• Cell Count
• Cell Proliferation
• Disease Models, Animal
• Dystrophin (deficiency)
• Flow Cytometry (methods)
• Gene Expression Regulation (genetics)
• Laminin (deficiency)
• Leukocyte Common Antigens (metabolism)
• Membrane Proteins (metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Inbred mdx
• Mice, Knockout
• Muscle Cells (pathology)
• Muscle, Skeletal
• Muscular Diseases (genetics, pathology, physiopathology)