Angiogenesis: The major abnormality of the keratin-14 IL-4 Transgenic mouse model of atopic dermatitis

被引:22
作者
Agha-Majzoub, R
Becker, RP
Schraufnagel, DE
Chan, LS
机构
[1] Univ Illinois, Dept Dermatol, Chicago, IL USA
[2] Univ Illinois, Dept Anat & Cell Biol, Chicago, IL USA
[3] Univ Illinois, Dept Pulm & Crit Care, Chicago, IL USA
[4] Univ Illinois, Dept Microbiol & Immunol, Chicago, IL 60680 USA
[5] VA W Side Med Ctr, Med Serv, Chicago, IL USA
关键词
angiogenesis; atopic dermatitis; claudin-5; confocal microscopy; electron microscopy; skin inflammation; tight junction;
D O I
10.1080/10739680591003297
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: Angiogenesis plays in 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 endothelial 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 ire 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.
引用
收藏
页码:455 / 476
页数:22
相关论文
共 48 条
[1]   PULMONARY LYMPHATICS AND THEIR SPATIAL RELATIONSHIP TO VENOUS SPHINCTERS [J].
AHARINEJAD, S ;
BOCK, P ;
FIRBAS, W ;
SCHRAUFNAGEL, DE .
ANATOMICAL RECORD, 1995, 242 (04) :531-544
[2]   ENDOTHELIAL FENESTRAL DIAPHRAGMS - A QUICK-FREEZE, DEEP-ETCH STUDY [J].
BEARER, EL ;
ORCI, L ;
SORS, P .
JOURNAL OF CELL BIOLOGY, 1985, 100 (02) :418-428
[3]   VEGF localisation in diabetic retinopathy [J].
Boulton, M ;
Foreman, D ;
Williams, G ;
McLeod, D .
BRITISH JOURNAL OF OPHTHALMOLOGY, 1998, 82 (05) :561-568
[4]   The cutaneous microcirculation: Ultrastructure and microanatomical organization [J].
Braverman, IM .
MICROCIRCULATION, 1997, 4 (03) :329-340
[5]  
Burri PH, 2002, MOL ASPECTS MED, V23, pS1
[6]   Mechanisms of angiogenesis and arteriogenesis [J].
Carmeliet, P .
NATURE MEDICINE, 2000, 6 (04) :389-395
[7]   Angiogenesis in health and disease [J].
Carmeliet, P .
NATURE MEDICINE, 2003, 9 (06) :653-660
[8]   Expression of interleukin-4 in the epidermis of transgenic mice results in a pruritic inflammatory skin disease: An experimental animal model to study atopic dermatitis [J].
Chan, LS ;
Robinson, N ;
Xu, LT .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2001, 117 (04) :977-983
[9]   Correlation of disease evolution with progressive inflammatory cell activation and migration in the IL-4 transgenic mouse model of atopic dermatitis [J].
Chen, L ;
Martinez, O ;
Venkataramani, P ;
Lin, SX ;
Prabhakar, BS ;
Chan, LS .
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2005, 139 (02) :189-201
[10]   Early up-regulation of Th2 cytokines and late surge of Th1 cytokines in an atopic dermatitis model [J].
Chen, L ;
Martinez, O ;
Overbergh, L ;
Mathieu, C ;
Prabhakar, BS ;
Chan, LS .
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2004, 138 (03) :375-387