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FIGURE 2 (See color insert) Atherosclerotic tissue is invested with PF4. (A) Photomicrograph (H&E stain) demonstrating the appearance of a group of foamy macrophages, which contain bubbly, vacuolated cytoplasm and indistinct nuclei (arrows). A giant cell is indicated by the arrowhead. (B) Photomicrograph of immunohistochemical staining for CD68, which is specific for cells of the macrophage lineage. Foamy macrophages (arrows) and a giant cell (arrowhead) is indicated. (C) Photomicrograph of immunohistochemical staining for CD41, specific for platelets. A small vessel filled with red blood cells and platelets serves as an internal positive control (inset). (D) This photomicrograph demonstrates the anti-PF4 staining the foamy macrophages. Note that the morphology of these cells is identical to those in panels (A-C), with vacuolated cytoplasm that stains for PF4 (arrows). (E) Photomicrograph demonstrating PF4 staining of an early atherosclerotic lesion from a carotid artery obtained at autopsy. The endothelium (arrowheads) and suben-dothelial macrophages (arrows) of an early lesion stain intensely positive with anti-PF4. Images are 40X (A-D) or 20X (E) original magnification. Abbreviation: PF4, platelet factor 4. Source: Reproduced from Pitsilos et al., 2003. (Thrombosis and Haemostasis, 2003, vol. 90, p. 1117, by copyright permission of the author and Schattauer GmbH.)

FIGURE 2 (See color insert) Atherosclerotic tissue is invested with PF4. (A) Photomicrograph (H&E stain) demonstrating the appearance of a group of foamy macrophages, which contain bubbly, vacuolated cytoplasm and indistinct nuclei (arrows). A giant cell is indicated by the arrowhead. (B) Photomicrograph of immunohistochemical staining for CD68, which is specific for cells of the macrophage lineage. Foamy macrophages (arrows) and a giant cell (arrowhead) is indicated. (C) Photomicrograph of immunohistochemical staining for CD41, specific for platelets. A small vessel filled with red blood cells and platelets serves as an internal positive control (inset). (D) This photomicrograph demonstrates the anti-PF4 staining the foamy macrophages. Note that the morphology of these cells is identical to those in panels (A-C), with vacuolated cytoplasm that stains for PF4 (arrows). (E) Photomicrograph demonstrating PF4 staining of an early atherosclerotic lesion from a carotid artery obtained at autopsy. The endothelium (arrowheads) and suben-dothelial macrophages (arrows) of an early lesion stain intensely positive with anti-PF4. Images are 40X (A-D) or 20X (E) original magnification. Abbreviation: PF4, platelet factor 4. Source: Reproduced from Pitsilos et al., 2003. (Thrombosis and Haemostasis, 2003, vol. 90, p. 1117, by copyright permission of the author and Schattauer GmbH.)

et al., 2003). Thus, HIT antibodies may modify the interactions of PF4 with diseased endothelium by (1) binding to PF4/proteoglycan complexes in atherosclerotic lesions, (2) inducing formation of platelet-leukocyte aggregates (Khairy et al., 2001), or (3) binding to circulating monocytes (Arepally et al., 2001; Pouplard et al., 2001), thereby increasing local inflammation and stimulating procoagulant processes.

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