Characterization of mac25/angiomodulin expression by high endothelial venule cells in lymphoid tissues and its identification as an inducible marker for activated endothelial cells.
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.
Usui
Takeo
T
Laboratory of Molecular and Cellular Recognition, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita 565-0871, Japan.
Murai
Toshiyuki
T
Tanaka
Toshiyuki
T
Yamaguchi
Kazuhito
K
Nagakubo
Daisuke
D
Lee
Chun Man
CM
Kiyomi
Masaaki
M
Tamura
Shinji
S
Matsuzawa
Yuji
Y
Miyasaka
Masayuki
M
D000818:Animals; D015415:Biomarkers; D002460:Cell Line; D016228:Endothelial Growth Factors / Q000378:metabolism; D004727:Endothelium / Q000378:metabolism*; D005786:Gene Expression Regulation; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008221:Lymphoid Tissue / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014699:Venules / Q000378:metabolism*
D015415:Biomarkers; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D009363:Neoplasm Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C086009:tumor-derived adhesion factor