Patrick Van Der Voorn, Janneke Tekstra, Rob H. J. Beelen, Cornelis P

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Expression of MCP-1 by Reactive Astrocytes in Demyelinating Multiple Sclerosis Lesions  Patrick Van Der Voorn, Janneke Tekstra, Rob H.J. Beelen, Cornelis P. Tensen, Paul Van Der Valk, Corline J.A. De Groot  The American Journal of Pathology  Volume 154, Issue 1, Pages 45-51 (January 1999) DOI: 10.1016/S0002-9440(10)65249-2 Copyright © 1999 American Society for Investigative Pathology Terms and Conditions

Figure 1 Cryostat sections from active demyelinating MS lesions (case S59/S116) and chronic active demyelinating MS lesions (case S276/S283). A: Histochemical staining with the neutral lipid marker Oil Red O (ORO) in an active demyelinating lesion. Abundant lipid-filled ORO-positive perivascular and parenchymal macrophages are distributed throughout the demyelinated lesion (arrowheads). B: Immunohistochemical staining with the macrophage marker KP-1 (CD68) in an active demyelinating MS lesion. Strong immunoreactivity for KP1 was detected in both foamy perivascular and parenchymal macrophages (arrowheads). C: A higher magnification shows the CD68-immunoreactive macrophages (arrowheads). D: Immunohistochemical staining with KP1 MAb in a chronic active demyelinated MS lesion. Fewer KP-1-positive parenchymal macrophages were detected in the lesion center, whereas in the hypercellular rim abundant KP1 immunoreactivity was present in macrophages (arrowheads). LC, lesion center; HR, hypercellular rim. E: ORO staining of a chronic active demyelinating lesion. Degraded lipid was detected in the parenchymal foamy macrophages in the hypercellular rim (arrowheads). F: Immunohistochemical staining with a GFAP-specific PAb. Hypertrophic, reactive astrocytes were detected in the lesion center and the hypercellular rim surrounding the demyelinated region (arrowheads). Magnification, ×100 (B and D), ×200 (A, E, and F), and ×400 (C). The American Journal of Pathology 1999 154, 45-51DOI: (10.1016/S0002-9440(10)65249-2) Copyright © 1999 American Society for Investigative Pathology Terms and Conditions

Figure 2 Cryostat sections from a normal control case (S49) and an active demyelinating MS lesion (case S116). A: Immunohistochemical staining with a MCP-1 MAb on white matter brain tissue from a normal control case. No MCP-1-immunoreactive cells were found. B: Immunohistochemical staining with a MCP-1 MAb of an active demyelinating MS lesion. Strong to intense immunoreactivity for MCP-1 was detected in virtually all reactive astrocytes (arrowheads) in the surrounding tissue of a perivascular infiltrate located within the demyelinated region. PI, perivascular infiltrate. In perivascular and parenchymal macrophages (arrows) no immunoreactivity for MCP-1 was found. C: Immunohistochemical staining with the astrocytic marker GFAP. Immunoreactivity for GFAP was detected in reactive astrocytes (arrowheads) equally distributed throughout the lesion site. D: No specific immunoreactivity was found in an active demyelinating MS lesion using an isotype-specific control MAb (IgG1). Magnification, ×200. The American Journal of Pathology 1999 154, 45-51DOI: (10.1016/S0002-9440(10)65249-2) Copyright © 1999 American Society for Investigative Pathology Terms and Conditions

Figure 3 Cryostat sections from a chronic active demyelinating MS lesion (case S276). A: Immunohistochemical staining with a MCP-1-specific MAb. Reactive astrocytes (arrowheads) stain positive for MCP-1. The immunoreactivity for MCP-1 in the reactive astrocytes became stronger with distance from the lesion center. LC, lesion center; HR, hypercellular rim. B: A reactive astrocyte (arrowhead) at the inner edge of the hypercellular rim of the lesion is strongly immunoreactive for MCP-1. C: Immunohistochemical staining with a GFAP-specific PAb on serial sections. Hypertrophic, reactive astrocytes (arrowheads) were detected in the lesion center and the hypercellular rim surrounding the demyelinated region (arrowheads). D: In the normal-appearing white matter (NAWM) adjacent to the hypercellular rim no immunoreactivity for MCP-1 was detected. Magnification, ×100 (A and B) and ×200 (B and D). The American Journal of Pathology 1999 154, 45-51DOI: (10.1016/S0002-9440(10)65249-2) Copyright © 1999 American Society for Investigative Pathology Terms and Conditions