BACKGROUND: Pericytes (PCs) are smooth muscle-like mural cells of capillaries and venules, which can synthesize matrix components and fibroblast-activating cytokines, and are thus potential mediators of pathological changes in scleroderma. In this study, alterations in microvessels were quantitatively imaged, taking PC into account for the first time. METHODS: Skin biopsies from systemic (12) and localized (14) scleroderma forms as well as age-, sex-, and body location-matched controls were examined with respect to capillary and venular densities as well as endothelial cell (EC) and PC counts using a newly developed (in respect of PC and EC) indirect collagen IV immunostaining-based method. RESULTS: Hyperplasia of the PC that doubled the microvascular PC density was the most conspicuous characteristic. In the capillaries of the upper dermal plexus of the periphery of the sclerotic zones, median ratios of PC : EC were 0.23 (controls 0.10) or 0.18 (controls 0.11) in systemic or localized scleroderma, respectively. Furthermore, an increase in capillary density in the upper dermal plexus could be demonstrated in the marginal zones of both types of disease. CONCLUSIONS: The observed PC increase in the peripheral zones of active disease supports the hypothesis of a vascular pathogenesis of scleroderma and directs the focus to microvascular PC.
BACKGROUND: Pericytes (PCs) are smooth muscle-like mural cells of capillaries and venules, which can synthesize matrix components and fibroblast-activating cytokines, and are thus potential mediators of pathological changes in scleroderma. In this study, alterations in microvessels were quantitatively imaged, taking PC into account for the first time. METHODS: Skin biopsies from systemic (12) and localized (14) scleroderma forms as well as age-, sex-, and body location-matched controls were examined with respect to capillary and venular densities as well as endothelial cell (EC) and PC counts using a newly developed (in respect of PC and EC) indirect collagen IV immunostaining-based method. RESULTS:Hyperplasia of the PC that doubled the microvascular PC density was the most conspicuous characteristic. In the capillaries of the upper dermal plexus of the periphery of the sclerotic zones, median ratios of PC : EC were 0.23 (controls 0.10) or 0.18 (controls 0.11) in systemic or localized scleroderma, respectively. Furthermore, an increase in capillary density in the upper dermal plexus could be demonstrated in the marginal zones of both types of disease. CONCLUSIONS: The observed PC increase in the peripheral zones of active disease supports the hypothesis of a vascular pathogenesis of scleroderma and directs the focus to microvascular PC.
Authors: Debendra Pattanaik; Monica Brown; Bradley C Postlethwaite; Arnold E Postlethwaite Journal: Front Immunol Date: 2015-06-08 Impact factor: 7.561