Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1992-6-23
pubmed:abstractText
Recent studies demonstrate that alternative splicing of mRNA from a single gene can produce two forms of vascular cell adhesion molecule 1 (VCAM-1): a six-immunoglobulin (Ig) domain form (VCAM-6D) and a seven-Ig domain form (VCAM-7D). Using a COS cell transient expression assay, we investigated whether VCAM-6D and VCAM-7D differ functionally in adhesion to the integrin VLA-4 (CD49d/CD29) on lymphoid cells. Binding of lymphoid cell lines and peripheral blood lymphocytes was completely blocked by VLA-4 monoclonal antibody (mAb) and one VCAM-1 mAb (4B9) to both VCAM-6D and VCAM-7D, whereas one VCAM-1 mAb (E1/6) completely blocked binding to VCAM-6D but only partially inhibited binding to VCAM-7D. We conclude that there is one VLA-4 binding site in the six Ig domains shared between VCAM-6D and VCAM-7D, and that the alternatively spliced domain 4 present in VCAM-7D provides a second VLA-4 binding site that is blocked by 4B9 but not the E1/6 mAb. We compared the inhibitory effects of anti-VCAM-1 and anti-VLA-4 mAbs on lymphoid cell adhesion to cultured human umbilical vein endothelial cells (HUVEC). The anti-VCAM-1 mAb 4B9 blocked the binding of PBL and lymphoid tumor cells to stimulated HUVEC better than the anti-VCAM-1 mAb E1/6. Because VCAM-7D is the predominant form of VCAM-1 expressed by stimulated endothelial cells, this difference in VCAM-1 mAb inhibition is attributed to lymphoid cell binding to VCAM-7D on stimulated HUVEC. Although the anti-VLA-4 mAb and anti-VCAM-1 mAb 4B9 equally inhibited PBL binding to stimulated HUVEC, mAb 4B9 inhibited the binding of two lymphoid cell lines significantly less than anti-VLA-4 mAb. Combination of 4B9 mAb with function-blocking antiserum to human fibronectin, a second known ligand for VLA-4, also failed to inhibit as much as anti-VLA-4 mAb. These findings suggest that adhesion of lymphoid cell lines through VLA-4 or other alpha 4 integrins may involve inducible counter-receptor(s) on endothelium distinct from either VCAM-1 or fibronectin. Time course experiments indicate that the fraction of alpha 4 integrin-dependent binding that can be blocked by anti-VCAM-1 mAb E1/6 rises and peaks within 2 h of tumor necrosis factor (TNF) stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-1675157, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-1676048, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-1691264, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-1693380, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-1695646, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-1697486, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-1697696, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-1699207, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-1702807, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-1704649, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-1707234, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-1707873, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-1709929, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-1710227, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-1713592, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-1715583, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-1715889, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-1716464, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-1717579, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-1861722, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-1970514, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-1974032, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-1980124, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-1990440, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-1997648, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-2040616, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-2083230, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-2108206, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-2139716, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-2142475, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-2188667, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-2219269, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-2295088, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-2430809, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-2527858, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-2551146, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-2588007, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-2688898, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-2825196, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-2896596, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-3091693, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-3109455, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-3134364, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-3492556, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-3525675, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-3555290, http://linkedlifedata.com/resource/pubmed/commentcorrection/1375259-6984191
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0022-1007
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
175
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1433-42
pubmed:dateRevised
2010-9-7
pubmed:meshHeading
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