All-trans-retinoic acid induces integrin-independent B-cell adhesion to ADAM disintegrin domains.
Cell adhesion is an integral aspect of immunity facilitating extravasation of immune cells during homing and activation. All -trans-Retinoic acid ( t-RA) regulates leukocyte differentiation, proliferation, and transmigration. However, the role of t-RA in immune cell adhesion is poorly defined. In this study, we evaluated the impact of t-RA and its metabolism on B and T cell adhesion. Specifically, we address the impact of t-RA on the adhesive properties of the human mature B and T cell lines RPMI 8866, Daudi and Jurkats. The effect of t-RA exposure on cell adhesion to vascular cell adhesion molecule-1 (VCAM-1), a well-established integrin counter receptor involved in immunity, and to nonconventional ADAM integrin ligands was assessed. We show for the first time that t-RA potently induces B cell adhesion in an integrin-independent manner to both VCAM-1 and select ADAM disintegrin domains. Using retinoid extraction and reverse-phase HPLC analysis, we identify the retinoid that is functionally responsible for this augmented adhesion. We also provide evidence that this novel t-RA adhesive response is not prototypical of lymphocytes since both Daudi and Jurkats do not alter their adhesive properties upon t-RA treatment. Further, the t-RA metabolic profiles between these lineages is distinct with 9- cis-retinoic acid being exclusively detected in Jurkat media. This study is the first to demonstrate that t-RA directly induces B cell adhesion in an integrin-independent manner and is not contingent upon t-RA metabolism.
Bridges
Lance C
LC
Department of Chemistry, University of Central Arkansas, Conway, Arkansas 72035, USA.
Lingo
Joshuah D
JD
Grandon
Rachel A
RA
Kelley
Melissa D
MD
D051722:ADAM Proteins / Q000737:chemistry / Q000378:metabolism*; D001402:B-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D006801:Humans; D016023:Integrins / Q000378:metabolism; D019169:Jurkat Cells; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014212:Tretinoin / Q000378:metabolism / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D016023:Integrins; D008562:Membrane Glycoproteins; D019010:Vascular Cell Adhesion Molecule-1; D014212:Tretinoin; D051722:ADAM Proteins; C438783:ADAM7 protein, human