title: 9-cis-retinoic acid promotes cell adhesion through integrin dependent and independent mechanisms across immune lineages.
abstract: Retinoids are essential in the proper establishment and maintenance of immunity. Although retinoids are implicated in immune related processes, their role in immune cell adhesion has not been well established. In this study, the effect of 9-cis-retinoic acid (9-cis-RA) on human hematopoietic cell adhesion was investigated. 9-cis-RA treatment specifically induced cell adhesion of the human immune cell lines HuT-78, NB4, RPMI 8866 and U937. Due to the prominent role of integrin receptors in mediating immune cell adhesion, we sought to evaluate if cell adhesion was integrin-dependent. By employing a variety of integrin antagonist including function-blocking antibodies and EDTA, we establish that 9-cis-RA prompts immune cell adhesion through established integrin receptors in addition to a novel integrin-independent process. The novel integrin-independent adhesion required the presence of retinoid and was attenuated by treatment with synthetic corticosteroids. Finally, we demonstrate that 9-cis-RA treatment of primary murine B-cells induces ex vivo adhesion that persists in the absence of integrin function. Our study is the first to demonstrate that 9-cis-RA influences immune cell adhesion through at least two functionally distinct mechanisms.
authors.affiliation: Department of Biochemistry and Molecular Biology, The Brody School of Medicine at East Carolina University, Greenville, NC 27834, USA.
authors.forename: Jarrett T
authors.initials: JT
authors.lastname: Whelan
authors.forename: Jianming
authors.initials: J
authors.lastname: Chen
authors.forename: Jabin
authors.initials: J
authors.lastname: Miller
authors.forename: Rebekah L
authors.initials: RL
authors.lastname: Morrow
authors.forename: Joshuah D
authors.initials: JD
authors.lastname: Lingo
authors.forename: Kaitlin
authors.initials: K
authors.lastname: Merrell
authors.forename: Saame Raza
authors.initials: SR
authors.lastname: Shaikh
authors.forename: Lance C
authors.initials: LC
authors.lastname: Bridges
mesh_terms: D000305:Adrenal Cortex Hormones / Q000378:metabolism; D000077556:Alitretinoin; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D005434:Flow Cytometry; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D000305:Adrenal Cortex Hormones; D000970:Antineoplastic Agents; D016023:Integrins; D018168:Receptors, Retinoic Acid; D011993:Recombinant Fusion Proteins; D000077556:Alitretinoin; D014212:Tretinoin