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Up-regulation of the hyaluronate receptor CD44 in canine distemper demyelinated plaques
S Alldinger1, S Fonfara, E Kremmer
1Institut für Veterinär-Pathologie, Justus-Liebig-Universität Giessen, Germany. Susanne.Alldinger@vetmed.uni-giessen.de
Insights
CD44 antigen expression increases on astrocytes during early canine distemper encephalitis (CDE) and shifts to immune cells in later stages. This study investigates CD44 changes in canine demyelinating disease.
Area of Science:
- Neuroimmunology
- Veterinary Pathology
- Cell Biology
Background:
- CD44 antigen (CD44) is a cell surface receptor upregulated in human multiple sclerosis.
- Astrocytes are primary targets of canine distemper virus (CDV).
- Canine distemper encephalitis (CDE) is a spontaneous demyelinating disease in dogs.
Purpose of the Study:
- To investigate CD44 expression and distribution in canine brains affected by CDE.
- To understand the role of CD44 in astrocyte activation and immune cell involvement during CDE.
Main Methods:
- Immunohistochemistry and immunoelectron microscopy on canine brain tissues from CDE cases and controls.
- Staining with antibodies against CD44, CDV nucleoprotein, glial fibrillary acidic protein (GFAP), and myelin basic protein (MBP).
Main Results:
- CD44 was upregulated on astrocytes in acute and subacute CDE plaques, correlating with GFAP.
- In chronic CDE, CD44 expression decreased with GFAP loss, but appeared on perivascular mononuclear cells.
- Immunoelectron microscopy showed CD44 on broadened astrocytic cell processes in CDE.
Conclusions:
- CD44 is upregulated on astrocytes in early CDE, serving as a marker for astrocyte activation.
- CD44 expression on immune cells in chronic CDE suggests a role in the late-stage immune response.
Abstract:
CD44 antigen (CD44), the principle cell surface receptor for hyaluronate, is up-regulated in the human demyelinating disease multiple sclerosis on fibrous astrocytes. As astrocytes are the main target cell of canine distemper virus (CDV), the consequences of a CDV infection on the CD44 expression and distribution in brains with spontaneous demyelinating canine distemper encephalitis (CDE) were of interest. Thirteen acute, 35 subacute, and 11 chronic plaques of nine dogs with immunohistologically confirmed CDE and brains of control dogs were included in the study. For light microscopy, 5-micron-thick serial sections were stained with H&E and incubated with monoclonal antibodies (mAbs) against CD44 and canine distemper virus nucleoprotein and polyclonal antibodies (pAbs) against glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP). For immunoelectron microscopy, 90-nm-thick sections were double stained with anti-GFAP and anti-CD44 mAbs to specify CD44-expressing structures. In controls, CD44 was diffusely distributed in the white matter and single meningeal cells exhibited a marginal expression of the antigen. In acute and more prominently in subacute demyelinating encephalitis, there was a plaque-associated up-regulation of CD44 which paralleled GFAP. In chronic demyelinating lesions, a reduction of CD44 associated with a loss of GFAP-positive astrocytes was noted. Additionally, in chronic plaques, CD44 was expressed on the cell membrane of perivascular mononuclear cells. Immunoelectron microscopically, in controls, CD44 was rarely demonstrated on astrocytic cell processes. In contrast, in brains with CDE CD44 was found on the cell membrane of broadened astrocytic cell processes. In summary, CD44 is up-regulated on astrocytes in the early phase of CDE and seems to represent a marker for the activation of immune cells in the late phase of the infection.