Enhanced expression of the P2X4 receptor in Duchenne muscular dystrophy correlates with macrophage invasion.
Following molecular and immunohistochemical analysis of the purinergic P2X4 receptor subunit in dystrophin-deficient muscle we have identified a distinct subpopulation of P2X4-positive cells infiltrating the dystrophic fibres. These cells were absent from normal muscle and rarely present in the dystrophic muscle taken before and after the onset of degeneration. We have identified these P2X4-positive cells as macrophages, demonstrating for the first time that human and mouse tissue macrophages express P2X4 in addition to P2X7 receptor subunits both in vitro and in situ. Moreover, we have demonstrated that the increase in the P2X4 expression is yet another feature of an inflammatory response identified in DNA arrays of dystrophic muscle. Immunohistochemical analysis failed to localise discernible expression of P2X4 protein in adult skeletal or cardiac muscle fibres, whilst myoblasts in culture expressed low levels of this subunit, as detected by RT-PCR and Western blotting. In light of the involvement of macrophages in the dystrophic process, the function of P2X receptors and their role in the Duchenne pathology as well as their potential role in therapeutic applications are discussed.
Institute of Biomedical and Biomolecular Sciences, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth PO1 2DT, UK.
Davy
D
Yeung
Riddhi
R
Kharidia
Susan C
SC
Brown
Dariusz C
DC
Górecki
D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008262:Macrophage Activation / Q000502:physiology*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009154:Mutation / Q000235:genetics; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000378:metabolism*; D058848:Receptors, Purinergic P2X4; D058486:Receptors, Purinergic P2X7; D015854:Up-Regulation / Q000235:genetics
C548226:P2RX4 protein, human; C546468:P2RX7 protein, human; C548227:P2rx4 protein, mouse; C546469:P2rx7 protein, mouse; D012333:RNA, Messenger; D018048:Receptors, Purinergic P2; D058848:Receptors, Purinergic P2X4; D058486:Receptors, Purinergic P2X7