title: CD14 is a ligand for the integrin alpha4beta1.
abstract: Cell adhesion mediated by the integrin alpha4beta1 plays a key role in many biological processes reflecting both the number and functional significance of alpha4beta1 ligands. The lipopolysaccharide (LPS) receptor, CD14, is a GPI-linked cell surface glycoprotein with a wide range of reported functions and associations, some of which overlap with that of alpha4beta1. This overlap led us to test the specific hypothesis that alpha4beta1 and CD14 interact directly. Jurkat T cells (alpha4beta1(+)) were found to adhere to a recombinant CD14-Fc protein via alpha4beta1, whilst K562 cells (alpha4beta1(-)) did not. However, stable reexpression of the alpha4-subunit conferred this ability. The adhesion of both cell types to CD14 displayed activation state-dependent binding very similar to the interaction of alpha4beta1 with its prototypic ligand, VCAM-1. In solid-phase assays, CD14-Fc bound to affinity-purified alpha4beta1 in a dose-dependent manner that was induced by activating anti-beta1 mAbs. Finally, in related experiments, JY cells (alpha4beta7(+)) were also found to attach to CD14-Fc in an alpha4-dependent manner. In summary, CD14 is a novel ligand for alpha4beta1, exhibiting similar activation-state dependent binding characteristics as other alpha4beta1 ligands. The biological relevance of this interaction will be the subject of further studies.
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, United Kingdom.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Humphries
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Humphries
mesh_terms: D000818:Animals; D019556:COS Cells; D002448:Cell Adhesion / Q000187:drug effects; D002522:Chlorocebus aethiops; D002846:Chromatography, Affinity; D006801:Humans; D039041:Integrin alpha4beta1 / Q000302:isolation & purification / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism; D019169:Jurkat Cells; D020014:K562 Cells; D008024:Ligands; D018950:Lipopolysaccharide Receptors / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D039041:Integrin alpha4beta1; D016023:Integrins; D008024:Ligands; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; C071777:integrin alpha4beta7