Gene expression profiling of mucosal addressin cell adhesion molecule-1+ high endothelial venule cells (HEV) and identification of a leucine-rich HEV glycoprotein as a HEV marker.
High endothelial venule (HEV) cells support lymphocyte migration from the peripheral blood into secondary lymphoid tissues. Using gene expression profiling of mucosal addressin cell adhesion molecule-1(+) mesenteric lymph node HEV cells by quantitative 3'-cDNA collection, we have identified a leucine-rich protein, named leucine-rich HEV glycoprotein (LRHG) that is selectively expressed in these cells. Northern blot analysis revealed that LRHG mRNA is approximately 1.3 kb and is expressed in lymph nodes, liver, and heart. In situ hybridization analysis demonstrated that the mRNA expression in lymph nodes is strictly restricted to the HEV cells, and immunofluorescence analysis with polyclonal Abs against LRHG indicated that the LRHG protein is localized mainly to HEV cells and possibly to some lymphoid cells surrounding the HEVs. LRHG cDNA encodes a 342-aa protein containing 8 tandem leucine-rich repeats of 24 aa each and has high homology to human leucine-rich alpha(2)-glycoprotein. Similar to some other leucine-rich repeat protein family members, LRHG can bind extracellular matrix proteins that are expressed on the basal lamina of HEVs, such as fibronectin, collagen IV, and laminin. In addition, LRHG binds TGF-beta. These results suggest that LRHG is likely to be multifunctional in that it may capture TGF-beta and/or other related humoral factors to modulate cell adhesion locally and may also be involved in the adhesion of HEV cells to the surrounding basal lamina.
Saito
Koichi
K
Laboratory of Molecular and Cellular Recognition, Osaka University Graduate School of Medicine, 2-2, Yamada-oka, Suita, 565-0871, Osaka, Japan.
Tanaka
Toshiyuki
T
Kanda
Hidenobu
H
Ebisuno
Yukihiko
Y
Izawa
Dai
D
Kawamoto
Shoko
S
Okubo
Kosaku
K
Miyasaka
Masayuki
M
D000595:Amino Acid Sequence; D000818:Animals; D015415:Biomarkers / Q000737:chemistry; D015815:Cell Adhesion Molecules; D002460:Cell Line; D002469:Cell Separation; D004729:Endothelium, Lymphatic / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D005109:Extracellular Matrix / Q000276:immunology / Q000378:metabolism; D020869:Gene Expression Profiling; D006023:Glycoproteins / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D007136:Immunoglobulins / Q000096:biosynthesis* / Q000235:genetics*; D007930:Leucine / Q000378:metabolism*; D000090263:Leucine-Rich Repeat Proteins; D008198:Lymph Nodes / Q000166:cytology / Q000378:metabolism; D008297:Male; D008643:Mesentery; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009088:Mucoproteins / Q000096:biosynthesis* / Q000235:genetics*; D011485:Protein Binding / Q000276:immunology; D011506:Proteins / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid; D016212:Transforming Growth Factor beta / Q000378:metabolism
D015415:Biomarkers; D015815:Cell Adhesion Molecules; D006023:Glycoproteins; D007136:Immunoglobulins; C015246:LRG1 protein, human; D000090263:Leucine-Rich Repeat Proteins; C504265:MADCAM1 protein, human; C489082:Madcam1 protein, mouse; D009088:Mucoproteins; D011506:Proteins; D016212:Transforming Growth Factor beta; D007930:Leucine