Roles of an extracellular matrix (ECM) receptor and ECM processing enzymes in demyelinating canine distemper encephalitis.
Canine distemper virus (CDV) belongs to the genus Morbillivirus of the Paramyxoviridae family. Due to the central nervous system (CNS) tropism of the virus and associated neuropathological changes, demyelinating canine distemper encephalitis (CDE) represents a relevant model for human demyelinating diseases like multiple sclerosis. The present review decribes the role of CD44 antigen (CD44), the principle cell surface receptor for hyaluronate and extracellular matrix (ECM) processing enzymes (matrix metalloproteinases [MMPs]) and their inhibitors (TIMPs) in the pathogenesis of demyelination. In acute and subacute CDE, a plaque-associated CD44 up-regulation is found that parallels astrocyte activation. Likewise, MMPs and TIMPs are prominently up-regulated in these lesions and are expressed mostly by astrocytes and microglia. In chronic lesions, CD44 expression declines together with the number of glial fibrillary acidic protein (GFAP) positive astrocytes. In addition, in this plaque type, CD44 is expressed on the cell membrane of perivascular mononuclear cells. In this phase, a decrease of MMP and TIMP expressions apart from MMP-11, -12, and -13 is obvious. In summary, CD44 and MMPs might be associated with the onset of demyelination and may interact to initiate ECM disturbances. Ligation of CD44 in the early phase may induce chemokines and cytokines and hence initiate and perpetuate the inflammatory process. In the chronic phase, it is conceivable that a MMP-TIMP imbalance may be the motor for lesion progression with a simultaneous influx of CD44-positive activated immune cells.
Alldinger
S
S
Institut für Pathologie, Stiftung Tierärztliche Hochschule Hannover, Hannover, Germany. Susanne.Alldinger@tiho-hannover.de
Gröters
S
S
Miao
Q
Q
Fonfara
S
S
Kremmer
E
E
Baumgärtner
W
W
D000818:Animals; D001253:Astrocytes / Q000276:immunology / Q000473:pathology; D020278:Demyelinating Autoimmune Diseases, CNS / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D004216:Distemper / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D004217:Distemper Virus, Canine / Q000276:immunology*; D004285:Dogs; D018792:Encephalitis, Viral / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D018960:Hyaluronan Receptors / Q000032:analysis / Q000096:biosynthesis; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation
D018960:Hyaluronan Receptors; D011956:Receptors, Cell Surface; C052131:extracellular matrix receptor; D020782:Matrix Metalloproteinases