title: Macrophages in inflammatory multiple sclerosis lesions have an intermediate activation status.
abstract: BACKGROUND
  Macrophages play a dual role in multiple sclerosis (MS) pathology. They can exert neuroprotective and growth promoting effects but also contribute to tissue damage by production of inflammatory mediators. The effector function of macrophages is determined by the way they are activated. Stimulation of monocyte-derived macrophages in vitro with interferon-γ and lipopolysaccharide results in classically activated (CA/M1) macrophages, and activation with interleukin 4 induces alternatively activated (AA/M2) macrophages.
  
  
  METHODS
  For this study, the expression of a panel of typical M1 and M2 markers on human monocyte derived M1 and M2 macrophages was analyzed using flow cytometry. This revealed that CD40 and mannose receptor (MR) were the most distinctive markers for human M1 and M2 macrophages, respectively. Using a panel of M1 and M2 markers we next examined the activation status of macrophages/microglia in MS lesions, normal appearing white matter and healthy control samples.
  
  
  RESULTS
  Our data show that M1 markers, including CD40, CD86, CD64 and CD32 were abundantly expressed by microglia in normal appearing white matter and by activated microglia and macrophages throughout active demyelinating MS lesions. M2 markers, such as MR and CD163 were expressed by myelin-laden macrophages in active lesions and perivascular macrophages. Double staining with anti-CD40 and anti-MR revealed that approximately 70% of the CD40-positive macrophages in MS lesions also expressed MR, indicating that the majority of infiltrating macrophages and activated microglial cells display an intermediate activation status.
  
  
  CONCLUSIONS
  Our findings show that, although macrophages in active MS lesions predominantly display M1 characteristics, a major subset of macrophages have an intermediate activation status.
authors: Department of Molecular Cell Biology and Immunology, VU University Medical Center, Van der Boechhorststraat 7, BT Amsterdam, 1081, The Netherlands.
authors: Daphne Y S
authors: DY
authors: Vogel
authors: Elly J F
authors: EJ
authors: Vereyken
authors: Judith E
authors: JE
authors: Glim
authors: Priscilla D A M
authors: PD
authors: Heijnen
authors: Martina
authors: M
authors: Moeton
authors: Paul
authors: P
authors: van der Valk
authors: Sandra
authors: S
authors: Amor
authors: Charlotte E
authors: CE
authors: Teunissen
authors: Jack
authors: J
authors: van Horssen
authors: Christine D
authors: CD
authors: Dijkstra
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D019013:CD40 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism* / Q000502:physiology; D008262:Macrophage Activation / Q000502:physiology; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology*
chemical_list: D019013:CD40 Antigens; D018836:Inflammation Mediators