CD14 is a ligand for the integrin α4β1

Cell adhesion mediated by the integrin α4β1 plays a key role in many biological processes reflecting both the number and functional significance of α4β1 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 α4β1. This overlap led us to test the specific hypothesis that α4β1 and CD14 interact directly. Jurkat T cells (α4β1+) were found to adhere to a recombinant CD14-Fc protein via α4β1, whilst K562 cells (α4β1-) did not. However, stable reexpression of the α4-subunit conferred this ability. The adhesion of both cell types to CD14 displayed activation state-dependent binding very similar to the interaction of α4β1 with its prototypic ligand, VCAM-1. In solid-phase assays, CD14-Fc bound to affinity-purified α4β1 in a dose-dependent manner that was induced by activating anti-β1 mAbs. Finally, in related experiments, JY cells (α4β7+) were also found to attach to CD14-Fc in an α4-dependent manner. In summary, CD14 is a novel ligand for α4β1, exhibiting similar activation-state dependent binding characteristics as other α4β1 ligands. The biological relevance of this interaction will be the subject of further studies. © 2007 Federation of European Biochemical Societies.