Microglial cell activation in demyelinating canine distemper lesions.
Microglia cells are the principal immune effector elements of the brain responding to any pathological event. To elucidate the possible role of microglia in initial non-inflammatory demyelination in canine distemper virus (CDV) infection, microglia from experimentally CDV infected dogs were isolated ex vivo by density gradient centrifugation and characterized immunophenotypically and functionally using flow cytometry. Results from dogs with demyelinating lesions were compared to results from recovered dogs and two healthy controls. CDV antigen could be detected in microglia of dogs with histopathologically confirmed demyelination. Microglia of these dogs showed marked upregulation of the surface molecules CD18, CD11b, CD11c, CD1c, MHC class I and MHC class II and a tendency for increased expression intensity of ICAM-1 (CD54), B7-1 (CD80), B7-2 (CD86), whereas no increased expression was found for CD44 and CD45. Functionally, microglia exhibited distinctly enhanced phagocytosis and generation of reactive oxygen species (ROS). It was concluded that in CDV infection, there is a clear association between microglial activation and demyelination. This strongly suggests that microglia contribute to acute myelin destruction in distemper.
Stein
Veronika M
VM
Department of Small Animal Medicine and Surgery, School of Veterinary Medicine Hannover, Bischofsholer Damm 15, D-30173 Hannover, Germany. Veronika.Stein@tiho-hannover.de
Czub
Markus
M
Schreiner
Nicole
N
Moore
Peter F
PF
Vandevelde
Marc
M
Zurbriggen
Andreas
A
Tipold
Andrea
A
D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism; D000956:Antigens, Viral; D001921:Brain / Q000473:pathology* / Q000821:virology; D002470:Cell Survival; D016009:Chi-Square Distribution; D003711:Demyelinating Diseases / Q000473:pathology* / Q000821:virology; D004216:Distemper / Q000473:pathology* / Q000821:virology; D004217:Distemper Virus, Canine / Q000472:pathogenicity; D004285:Dogs; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D007150:Immunohistochemistry; D008285:Major Histocompatibility Complex / Q000502:physiology; D008297:Male; D017628:Microglia / Q000473:pathology* / Q000821:virology; D010587:Phagocytosis / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D018709:Statistics, Nonparametric
D000944:Antigens, Differentiation, B-Lymphocyte; D000956:Antigens, Viral; D017382:Reactive Oxygen Species