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International Immunology, Vol. 14, No. 11, pp. 1273-1282, November 2002
© 2002 Japanese Society for Immunology

Characterization of mac25/angiomodulin expression by high endothelial venule cells in lymphoid tissues and its identification as an inducible marker for activated endothelial cells

Takeo Usui1, Toshiyuki Murai1, Toshiyuki Tanaka1, Kazuhito Yamaguchi3, Daisuke Nagakubo1, Chun Man Lee1, Masaaki Kiyomi1, Shinji Tamura2, Yuji Matsuzawa2 and Masayuki Miyasaka1

1 Laboratory of Molecular and Cellular Recognition, and 2 Department of Internal Medicine and Molecular Science, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita 565-0871, Japan 3 Institute of Laboratory Animals, Yamaguchi University School of Medicine, Ube 755-8505, Japan

Correspondence to: M. Miyasaka; E-mail: mmiyasak{at}orgctl.med.osaka-u.ac.jp
Transmitting editor: T. Watanabe

Previous results have indicated that mac25/angiomodulin (AGM) is expressed in lymph node (LN) high endothelial venules (HEV), the specialized venules that support efficient lymphocyte transendothelial migration. How mac25/AGM’s endothelial expression pattern is regulated in situ remains unknown. Here, we demonstrate that in mouse LN blood vessels, including HEV, mac25/AGM is localized, unlike previous reports, not to the luminal or lateral regions bordering the endothelial cells (EC), but exclusively to the basal lamina that is in direct association with EC. In the spleen, mac25/AGM was expressed in the vascular basal lamina, in direct association with smooth muscle cells and pericytes, but not with EC. In addition, we report herein that mac25/AGM is an inducible marker for activated EC. In inflamed tissues, mac25/AGM expression was strongly induced in the abluminal region of blood vessels. In vitro, mac25/AGM was readily induced in EC upon activation with pro-inflammatory cytokines such as tumor necrosis factor-{alpha}, indicating that mac25/AGM is an activated EC marker. mac25/AGM binds vascular endothelial growth factor and, together with its strict abluminal localization, it is suggested that mac25/AGM has a specific function(s) in the subendothelium of activated blood vessels such as capturing humoral factors produced in the vicinity of HEV.

Keywords: high endothelial venule, lymphocyte homing, vascular endothelial growth factor


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D. Nagakubo, T. Murai, T. Tanaka, T. Usui, M. Matsumoto, K. Sekiguchi, and M. Miyasaka
A High Endothelial Venule Secretory Protein, Mac25/Angiomodulin, Interacts with Multiple High Endothelial Venule-Associated Molecules Including Chemokines
J. Immunol., July 15, 2003; 171(2): 553 - 561.
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