Modulation of integrin α4β1 by ADAM28 promotes lymphocyte adhesion and transendothelial migration

McGinn, Owen J., English, William R. ORCID:, Roberts, Stephanie, Ager, Ann, Newham, Peter and Murphy, Gillian (2011) Modulation of integrin α4β1 by ADAM28 promotes lymphocyte adhesion and transendothelial migration. Cell Biology International, 35 (10). pp. 1043-1053. ISSN 1065-6995

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ADAMs (a disintegrin and metalloproteinase) are a family of type I transmembrane glycoproteins related to snake venom metalloproteases and disintegrins. They are regulatory proteins that modulate intercellular adhesion and the bioavailability of growth factors, and have been implicated in many disease states, including cancer, immunity and inflammation. One member of the ADAM family, ADAM28, has been reported to bind to the integrin α4β1 in humans; however, the distribution of ADAM28 and the biological consequences of ADAM28–α4β1 interactions are yet to be fully elucidated. The expression of ADAM28 in human and murine tissues was examined by multiple Affymetrix microarray analyses, real-time RT—PCR (reverse transcription—PCR) and immunohistochemical staining. We found that ADAM28 has a relatively restricted expression pattern in mouse and human and is highly expressed in the B-lymphocyte lineage, including chronic lymphocytic leukaemic B-cells. The murine B-lymphoma line L1-2 and recombinant soluble murine ADAM28 were used to investigate ADAM28–α4β1 interactions. Our data reveal that ADAM28 binding to α4β1 is typical of integrin—ligand interactions, since it is attenuated by anti-functional integrin antibodies, and is enhanced by Mn2+ and the integrin mAb (monoclonal antibody) 9EG7. However, a key finding was that soluble ADAM28 unexpectedly enhanced α4β1-dependent cell adhesion to VCAM-1 (vascular cell adhesion molecule-1). In so doing ADAM28 was able to influence lymphocyte adhesion to, and migration through, endothelial monolayers, suggesting a physiological role for ADAM28 in regulating the specific spatial and temporal transendothelial migration of lymphocytes.

Item Type: Article
Uncontrolled Keywords: sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Faculty of Science > School of Biological Sciences
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Depositing User: LivePure Connector
Date Deposited: 15 Dec 2022 11:31
Last Modified: 19 Oct 2023 03:30
DOI: 10.1042/CBI20100885

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