| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
2 From the Divisions of Newborn Medicine and 6 Pediatric Hematology and Oncology, Children’s Hospital, Boston, Massachusetts; the 3 Retina Research Laboratory, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts; the 4 Department of Vitreoretinal Surgery, Center for Ophthalmology, Cologne, Germany; the 5 Department of Pediatric Oncology, Medical School Hannover, Hannover, Germany; and 7 Center for Blood Research and Department of Pathology, Harvard Medical School, Boston, Massachusetts.
PURPOSE. Leukocyte endothelial interactions are a key feature of ocular angiogenesis but also play a role in nonproliferative vascular alterations as are found in early diabetes or uveitis. The adhesion of leukocytes to endothelial cells during inflammation is a multistep process that involves leukocyte rolling, adhesion, and extravasation mediated by selectins, cell adhesion molecules (CAMs), integrins, and chemokines. Heparan sulfate (HS) is known to bind to and modify the function of these molecules under physiological conditions. In this study, the role of the HS proteoglycan syndecan-1 in mediating leukocyte–endothelial interactions in the ocular vasculature was investigated.
METHODS. Mice carrying a deletion in the gene encoding the cell surface HS proteoglycan syndecan-1 (sdc1) were used to study the interactions of leukocytes and endothelial cells in vivo, using a perfusion technique with FITC-coupled ConA and intravital microscopy.
RESULTS. In a retina perfusion model, Sdc1-/- mice showed increased leukocyte adhesion that was largely attributable to the leukocytes. Intravital microscopy studies revealed a dramatic increase in adhesion after tumor necrosis factor (TNF)-
treatment of sdc1-/- mice compared with similarly treated wild-type mice. The higher degree of leukocyte adhesion may account for the increase in inflammation-mediated corneal angiogenesis observed in sdc1-/- mice.
CONCLUSIONS. The results indicate a role for syndecan-1 as a negative regulator of leukocyte-mediated inflammatory responses. Thus, syndecan-1 could have use as a target for prevention of pathologic leukocyte–endothelial interactions in angiogenesis and inflammation.
This article has been cited by other articles:
|
|
 |
|
  A M Patterson, A Cartwright, G David, O Fitzgerald, B Bresnihan, B A Ashton, and J Middleton Differential expression of syndecans and glypicans in chronically inflamed synovium Ann Rheum Dis, May 1, 2008; 67(5): 592 - 601. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Stepp, Y. Liu, S. Pal-Ghosh, R. A. Jurjus, G. Tadvalkar, A. Sekaran, K. LoSicco, L. Jiang, M. Larsen, L. Li, et al. Reduced migration, altered matrix and enhanced TGFbeta1 signaling are signatures of mouse keratinocytes lacking Sdc1 J. Cell Sci., August 15, 2007; 120(16): 2851 - 2863. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Fuster, L. Wang, J. Castagnola, L. Sikora, K. Reddi, P. H.A. Lee, K. A. Radek, M. Schuksz, J. R. Bishop, R. L. Gallo, et al. Genetic alteration of endothelial heparan sulfate selectively inhibits tumor angiogenesis J. Cell Biol., May 7, 2007; 177(3): 539 - 549. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Vanhoutte, M. W.M. Schellings, M. Gotte, M. Swinnen, V. Herias, M. K. Wild, D. Vestweber, E. Chorianopoulos, V. Cortes, A. Rigotti, et al. Increased Expression of Syndecan-1 Protects Against Cardiac Dilatation and Dysfunction After Myocardial Infarction Circulation, January 30, 2007; 115(4): 475 - 482. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. W. Yip, M. Smollich, and M. Gotte Therapeutic value of glycosaminoglycans in cancer. Mol. Cancer Ther., September 1, 2006; 5(9): 2139 - 2148. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. X Zhang, J. J Wang, G. Gao, K. Parke, and J.-x. Ma Pigment epithelium-derived factor downregulates vascular endothelial growth factor (VEGF) expression and inhibits VEGF-VEGF receptor 2 binding in diabetic retinopathy. J. Mol. Endocrinol., August 1, 2006; 37(1): 1 - 12. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. R. Taylor and R. L. Gallo Glycosaminoglycans and their proteoglycans: host-associated molecular patterns for initiation and modulation of inflammation FASEB J, January 1, 2006; 20(1): 9 - 22. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Haynes III, F. Ruda, J. Oliver, A. N. Hamood, J. A. Griswold, P. W. Park, and K. P. Rumbaugh Syndecan 1 Shedding Contributes to Pseudomonas aeruginosa Sepsis Infect. Immun., December 1, 2005; 73(12): 7914 - 7921. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Tkachenko, J. M. Rhodes, and M. Simons Syndecans: New Kids on the Signaling Block Circ. Res., March 18, 2005; 96(5): 488 - 500. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Ledin, W. Staatz, J.-P. Li, M. Gotte, S. Selleck, L. Kjellen, and D. Spillmann Heparan Sulfate Structure in Mice with Genetically Modified Heparan Sulfate Production J. Biol. Chem., October 8, 2004; 279(41): 42732 - 42741. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Elenius, M. Gotte, O. Reizes, K. Elenius, and M. Bernfield Inhibition by the Soluble Syndecan-1 Ectodomains Delays Wound Repair in Mice Overexpressing Syndecan-1 J. Biol. Chem., October 1, 2004; 279(40): 41928 - 41935. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Abrink, M. Grujic, and G. Pejler Serglycin Is Essential for Maturation of Mast Cell Secretory Granule J. Biol. Chem., September 24, 2004; 279(39): 40897 - 40905. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. W. Mulivor and H. H. Lipowsky Inflammation- and ischemia-induced shedding of venular glycocalyx Am J Physiol Heart Circ Physiol, May 1, 2004; 286(5): H1672 - H1680. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. GOTTE Syndecans in inflammation FASEB J, April 1, 2003; 17(6): 575 - 591. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Stepp, H. E. Gibson, P. H. Gala, D. D. Sta. Iglesia, A. Pajoohesh-Ganji, S. Pal-Ghosh, M. Brown, C. Aquino, A. M. Schwartz, O. Goldberger, et al. Defects in keratinocyte activation during wound healing in the syndecan-1-deficient mouse J. Cell Sci., January 12, 2002; 115(23): 4517 - 4531. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
