Back to Search
Start Over
A high endothelial venule secretory protein, mac25/angiomodulin, interacts with multiple high endothelial venule-associated molecules including chemokines.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2003 Jul 15; Vol. 171 (2), pp. 553-61. - Publication Year :
- 2003
-
Abstract
- We previously reported that mac25/angiomodulin (AGM), a 30-kDa secretory protein, is abundantly expressed in high endothelial venules (HEVs), which play a crucial role in lymphocyte trafficking to the lymph nodes and Peyer's patches. We report that mac25/AGM interacts preferentially with certain molecules that are expressed in or around HEVs. In particular, mac25/AGM interacted with not only the extracellular matrix proteins and glycosaminoglycans that are expressed in most blood vessels including HEVs, but also with some chemokines that are implicated in the regulation of lymphocyte trafficking, such as the secondary lymphoid-tissue chemokine (SLC; CCL21), IFN-gamma-inducible protein 10 (IP-10; CXCL10), and RANTES (CCL5). The binding of mac25/AGM to SLC and IP-10 was dose-dependent and saturable. The binding to IP-10 could be inhibited by SLC but not by a non-mac25/AGM-binding chemokine, EBI1-ligand chemokine (ELC; CCL19). Interestingly, mac25/AGM failed to interact with 18 other chemokines, suggesting that it binds to certain chemokines preferentially. Immunohistochemical analysis indicated that mac25/AGM colocalizes at least partially with SLC and IP-10 at the basal lamina of HEVs. Upon binding with mac25/AGM, SLC and IP-10 retained all their Ca(2+)-signaling activity in vitro, suggesting that mac25/AGM can hold and present chemokines in the basal lamina of HEVs. These results imply that mac25/AGM plays a multifunctional role, serving not only as an adhesion protein to interact with glycosaminoglycans and extracellular matrix proteins but also as a molecule to present chemokines so that lymphocytes extravasating through HEVs receive further directional cues subsequent to the luminal encounter with lymphoid chemokines.
- Subjects :
- Amino Acid Sequence
Animals
Binding Sites immunology
Calcium Signaling immunology
Carrier Proteins physiology
Cell Line
Chemokine CCL21
Chemokine CXCL10
Chemokines physiology
Chemokines, CC metabolism
Chemokines, CXC metabolism
Chemotaxis, Leukocyte immunology
Endothelium, Lymphatic blood supply
Endothelium, Lymphatic physiology
Extracellular Matrix Proteins biosynthesis
Extracellular Matrix Proteins metabolism
Female
Glycosaminoglycans biosynthesis
Glycosaminoglycans metabolism
Mice
Mice, Inbred C57BL
Molecular Sequence Data
Neoplasm Proteins physiology
Protein Binding immunology
Venules physiology
Carrier Proteins metabolism
Chemokines metabolism
Endothelium, Lymphatic metabolism
Insulin-Like Growth Factor Binding Proteins
Neoplasm Proteins metabolism
Venules metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 171
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 12847218
- Full Text :
- https://doi.org/10.4049/jimmunol.171.2.553