CD14 is a ligand for the integrin α4β1

Cell adhesion mediated by the integrin alpha 4 beta 1 plays a key role in many biological processes reflecting both the number and functional significance of alpha 4 beta 1 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 alpha 4 beta 1. This overlap led us to test the specific hypothesis that alpha 4 beta 1 and CD14 interact directly. Jurkat T cells (alpha 4 beta 1(+)) were found to adhere to a recombinant CD14-Fc protein via alpha 4 beta 1, whilst K562 cells (alpha 4 beta 1(-)) did not. However, stable reexpression of the alpha 4-subunit conferred this ability. The adhesion of both cell types to CD14 displayed activation state-dependent binding very similar to the interaction of alpha 4 beta 1 with its prototypic ligand, VCAM-1. In solid-phase assays, CD14-Fc bound to affinity-purified alpha 4 beta 1 in a dose-dependent manner that was induced by activating anti-PI mAbs. Finally, in related experiments, JY cells (alpha 4 beta 7(+)) were also found to attach to CD14-Fc in an alpha 4-dependent manner. In summary, CD14 is a novel ligand for alpha 4 beta 1, exhibiting similar activation-state dependent binding characteristics as other alpha 4 beta 1 ligands. The biological relevance of this interaction will be the subject of further studies. (c) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.