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PMID: 1370496 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A monoclonal antibody to beta 1 integrin (CD29) stimulates VLA-dependent adherence of leukocytes to human umbilical vein endothelial cells and matrix components.

The Journal of cell biology ·Vol. 116 ·No. 2 ·1992-01-00 ·Pages 499-509

Kovach NL, Carlos TM, Yee E, Harlan JM

Abstract

The leukocyte beta 1 integrin receptor very late activation antigen-4 (VLA-4) (alpha 4 beta 1, CD49d/CD29) binds to vascular cell adhesion molecule-1 (VCAM-1) expressed on cytokine-activated endothelium. A mAb designated 8A2 was identified that stimulated the binding of U937 cells to CHO cells transfected with VCAM-1 cDNA but not endothelial-leukocyte adhesion molecule or CD4 cDNA. mAb 8A2 also rapidly stimulated the adherence of peripheral blood lymphocytes (PBLs) to VCAM-1-transfected CHO cells or recombinant human tumor necrosis factor-treated human umbilical vein endothelial cells. mAb 8A2-stimulated binding of PBL was inhibited by mAbs to VLA-4 or VCAM-1. Surface expression of VLA-4 was not altered by mAb 8A2 treatment and monovalent Fab fragments of mAb 8A2 were active. Immunoprecipitation studies reveal that mAb 8A2 recognizes beta 1-subunit (CD29) of integrin receptors. In contrast to mAbs directed to VLA-4 alpha-subunit (alpha 4, CD49d), mAb 8A2 did not induce homotypic aggregation of PBL. Additionally, mAb 8A2 stimulated adherence of PBL and hematopoietic cell lines to purified matrix components laminin and fibronectin. This binding was blocked by mAbs to the VLA alpha-subunits alpha 6 (CD49f), or alpha 5 (CD49e) and alpha 4 (CD49d), respectively. We conclude that mAb 8A2 modulates the affinity of VLA-4 and other leukocyte beta 1 integrins, and should prove useful in studying the regulation of beta 1 integrin function.

MeSH Terms
Animals Antibodies, Monoclonal Antigens, CD/physiology CHO Cells Cell Adhesion Cell Adhesion Molecules/metabolism Cricetinae Endothelium, Vascular/cytology Energy Metabolism Extracellular Matrix/physiology Fibronectins/metabolism Humans In Vitro Techniques Integrin beta1 Integrins/physiology Laminin/metabolism Leukocytes/cytology Receptors, Very Late Antigen/physiology Recombinant Proteins Vascular Cell Adhesion Molecule-1
Chemicals
Antibodies, Monoclonal Antigens, CD Cell Adhesion Molecules Fibronectins Integrin beta1 Integrins Laminin Receptors, Very Late Antigen Recombinant Proteins Vascular Cell Adhesion Molecule-1
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Kovach N L
University of Washington, School of Medicine, Division of Hematology, Seattle 98195.
Carlos T M
Yee E
Harlan J M
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52 references, click to expand
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.116.2.499
Published
1992-01-00
Pages
499-509
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2289280
Subset
IM
Grants
NHLBI NIH HHS · HL-07093-16 · United States
NHLBI NIH HHS · HL-18645 · United States
External Links
PubMed source DOI: 10.1083/jcb.116.2.499 PMC Full Text View journal details
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