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Original

Angiogenesis: The Major Abnormality of the Keratin-14 IL-4 Transgenic Mouse Model of Atopic Dermatitis

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Pages 455-476 | Received 24 Nov 2004, Accepted 07 Mar 2005, Published online: 10 Jul 2009
 

Abstract

Objective: Angiogenesis plays an important role in psoriasis, but its role in atopic dermatitis is unknown. The authors examined the dermal microvasculature of an IL-4 transgenic mouse model of atopic dermatitis to determine whether angiogenesis was present.

Methods: Transmission and scanning electron microscopy and confocal microscopy studies were performed.

Results: Transmission electron microscopy showed sprouting, transcapillary pillars of intussusception, thickened endothelial cells with large nuclei, and increased interendothelial junctional cleft number and length. Compared to nontransgenic littermates, there was a significant increase in the lengths and numbers of the interendothelial junctional clefts, along with a decrease in the length ratios of tight junction to interendothelial junctional clefts in both the early and late disease stages. In the early and late skin lesions, scanning electron microscopy of vascular corrosion casts showed disorganization of the capillary network hierarchy with increased density of capillary sprouts. Confocal microscopy of the animals with early and late skin lesions showed significant reduction in tight junction protein claudin-5.

Conclusions: Angiogenesis is the major pathologic feature in this model of atopic dermatitis. The chronic skin inflammation is intertwined with and may cause the angiogenesis, but the angiogenesis itself is likely to be important in this disease process.

The authors thank Shiganori Okada, PhD, DDS (Department of pulmonary and critical care, UIC, Chicago, IL) for his technical support and knowledge of the vascular casting method and scanning electron microscopy, Mei Ling Chen, MD (Confocal Microscopy Core Facility, UIC, Chicago, IL) for her tremendous assistance in confocal microscopy, Shao-Xia Lin (Department of Dermatology UIC, Chicago, IL) for her outstanding technical skills, Lin Chen, MD, PhD (Department of Dermatology, UIC, Chicago, IL) for his overall support, and the electron microscopy facility at the University of Illinois at Chicago. This work was supported by NIH grant R03AR47634.

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