Persistent activation of omentum influences the pattern of muscular lesion in the mdx diaphragm.
The mdx (X chromosome-linked muscular dystrophy) mouse develops a multi-staged disorder characterized by muscle degeneration and reactive fibrosis. Skeletal muscles of mdx mice are not equally susceptible to degeneration. The aim of this study was to verify whether the intense remodeling of the mdx diaphragm could be attributed to influences from the peritoneal microenvironment and omentum, a lymphohematopoietic tissue rich in progenitor cells and trophic factors. At ages corresponding to increased muscular regeneration (12 weeks) and activation of fibrosis (24 weeks), the mdx omentum exhibited (1) morphological and functional characteristics of activation with enlarged milk-spots, an accumulation of CD4(+), CD8(+) and CD19(+)B220(+) B lymphocytes; (2) the formation of clusters positive for proliferating cell nuclear antigen, mainly in B220(+)-rich areas organized in a follicular structure with a germinative center without any challenge by external antigen inducers; (3) clusters with cells positive for fibroblast growth factor-2, numerous Sca-1(+)CD3(-)CD19(-)Mac-1(-) progenitor cells and increased CD4(+), CD8(+) and CD3(+)NK1.1(+) cells in the peritoneal cavity. Omentectomy reduced areas with F4/80(+) inflammatory infiltrate the activity of matrix metalloproteases 9 and 2, collagen deposition and areas with regenerating myofibers in the diaphragm. Thus, persistent activation of the omentum influences the pattern of inflammation and regeneration of the mdx diaphragm partly via the activation of progenitor cells and the production of growth factors that influence the physiopathology of the muscular tissue remodeling.
Department of Immunobiology, Fluminense Federal University, Niterói, RJ 24 020 141, Brazil.
Douglas Florindo
DF
Pinheiro
Rafael F
RF
da Silva
Lian P
LP
Carvalho
Eustaquio L
EL
Paiva-Oliveira
Ricardo S
RS
Pereira
Paulo Emilio C
PE
Leite
Maria
M
de Fátima Pinho
Thereza
T
Quirico-Santos
Jussara
J
Lagrota-Candido
D000818:Animals; D003964:Diaphragm / Q000473:pathology*; D005434:Flow Cytometry; D008214:Lymphocytes / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D009137:Muscular Dystrophy, Animal / Q000473:pathology*; D009852:Omentum / Q000276:immunology / Q000473:pathology* / Q000601:surgery; D010529:Peritoneal Cavity / Q000473:pathology; D013234:Stem Cells / Q000166:cytology