title: Nav1.5 sodium channels in macrophages in multiple sclerosis lesions.
abstract: BACKGROUND
  Macrophages are dynamic participants in destruction of white matter in active multiple sclerosis (MS) plaques. Regulation of phagocytosis and myelin degradation along endosomal pathways in macrophages is highly-orchestrated and critically-dependent upon acidification of endosomal lumena. Evidence from in vitro studies with macrophages and THP-1 cells suggests that sodium channel Nav1.5 is present in the limiting membrane of maturing endosomes where it plays a prominent role in the accumulation of protons. However, a contribution of the Nav1.5 channel to macrophage-mediated events in vivo has not been demonstrated.
  
  
  METHODS
  We examined macrophages within active MS lesions by immunohistochemistry to determine whether Nav1.5 is expressed in these cells in situ and, if expressed, whether it is localized to specific compartments along the endocytic pathway.
  
  
  RESULTS
  Our results demonstrate that Nav1.5 is expressed within macrophages in active MS lesions, and that it is preferentially expressed in late endosomes and phagolysosomes (Rab7(+), LAMP-1(+)), and sparsely expressed in early (EEA-1(+)) endosomes. Triple-immunolabeling studies showed localization of Nav1.5 within Rab7(+) endosomes containing proteolipid protein, a myelin marker, in macrophages within active MS plaques.
  
  
  CONCLUSIONS
  These observations support the suggestion that Nav1.5 contributes to the phagocytic pathway of myelin degradation in macrophages in vivo within MS lesions.
authors.affiliation: Department of Neurology and Paralyzed Veterans of America Center for Neuroscience and Regeneration Research, Yale University School of Medicine, USA. joel.black@yale.edu
authors.forename: Joel A
authors.initials: JA
authors.lastname: Black
authors.forename: Jia
authors.initials: J
authors.lastname: Newcombe
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Waxman
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000378:metabolism*; D016022:Case-Control Studies; D004705:Endocytosis / Q000502:physiology; D011992:Endosomes / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000378:metabolism*; D010587:Phagocytosis / Q000502:physiology; D010588:Phagosomes / Q000378:metabolism
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human