Characterization of Lymphocyte-Dependent Angiogenesis Using a SCID Mouse: Human Skin Model of Psoriasis  Brian J. Nickoloff  Journal of Investigative Dermatology Symposium Proceedings  Volume 5, Issue 1, Pages 67-73 (December 2000) DOI: 10.1046/j.1087-0024.2000.00006.x Copyright © 2000 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Angiogenic tissue reaction in engrafted prepsoriatic human skin transplanted onto SCID mice. When orthotopically transplanted skin is injected with saline, no angiogenesis is present (A), but 2 weeks after injection of activated immunocytes the human dermis contains numerous small and large blood vessels reflecting a local angiogenic tissue response that accompanies the other clinical and microscopic changes characteristic of a bona fide plaque of psoriasis (B). Journal of Investigative Dermatology Symposium Proceedings 2000 5, 67-73DOI: (10.1046/j.1087-0024.2000.00006.x) Copyright © 2000 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Differential expression of αvβ3 versus αvβ5 integrins in NN, PN, and chronic psoriatic plaques (PP skin), as well as acute psoriatic lesions created using the SCID mouse model. Immunoperoxidase staining; Vectastain (anti-αvβ3 integrin MoAb, MoAb 1976, and anti-αVβ5 integrin MoAb, MoAb 1961; anti-ELAM-1; CD62E). 3-amino-4-ethylcarbazole as chromagen producing positive red reaction product. (A) αvβ3 expression is absent in NN skin, but is focally present in PN skin and diffusely positive in endothelial cells in chronic PP skin. An acute psoriatic lesion created by injecting activated autologous immunocytes into engrafted PN skin reveals endothelial cell positivity for αvβ3 integrin (panel labelled SCID). (B) αvβ5 expression is focally present on upper dermal dendritic cells, and on basal keratinocytes and dermal dendritic cells in PN skin. In a chronic psoriatic plaque, while perivascular and interstitial dendritic cells are αvβ5 positive, the endothelial cells are negative. An acute psoriatic lesion created on a SCID mouse (far right panel) has strong and diffuse dendritic cell αvβ5 expression, but no endothelial cell positivity. Inset reveals ELAM-1 expression on microvascular endothelial cells. Journal of Investigative Dermatology Symposium Proceedings 2000 5, 67-73DOI: (10.1046/j.1087-0024.2000.00006.x) Copyright © 2000 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 Psoriatic plaque contains a rich admixture of macrophages and dendritic cells. The macrophage population includes a pan-macrophage marker CD14, macrophages with classical activation markers (i.e., CD16, CD32) as well as alternatively activated macrophages (CD163, mannose receptor). In addition, there are epidermal and dermal dendritic cells expressing CD1a, CD80, and CD83, indicating various degrees of maturation of these professional antigen-presenting cells. Journal of Investigative Dermatology Symposium Proceedings 2000 5, 67-73DOI: (10.1046/j.1087-0024.2000.00006.x) Copyright © 2000 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 4 Model for understanding the cellular and molecular basis for the angiogenic tissue reaction in psoriasis highlighting the role of activated immunocytes producing cytokines that trigger neovascularization of the dermis. The upper panels depict the microscopic and clinical appearance of symptomless skin engrafted onto a SCID mouse, and the subsequent psoriatic plaque that is created following injection of activated immunocytes (inset includes prominent neovascularization of dermis underlying newly created psoriatic plaque). The lower panels represent a model in which the intradermal injected activated immunocytes (i.e., natural killer T cells) produce cytokines such as IFN-γ that are accompanied by several keratinocyte-derived, macrophage-derived, and dermal dendrocyte-derived pro-angiogenic factors. The net result of this cytokine network is activation and proliferation of αVβ3 integrin positive endothelial cells. Journal of Investigative Dermatology Symposium Proceedings 2000 5, 67-73DOI: (10.1046/j.1087-0024.2000.00006.x) Copyright © 2000 The Society for Investigative Dermatology, Inc Terms and Conditions