MAC-1 (CDLLB CD18) IS AN OLIGODEOXYNUCLEOTIDE-BINDING PROTEIN/

We have studied the interactions of phosphodiester and phosphorothioat e oligodeoxynucleotides with Mac-1 (CD11b/CD18; alpha M beta 2), a hep arin-binding integrin found predominately on the surface of polymorpho nuclear leukocytes (PMNs), macrophages and natural killer cells. Bindi ng of a homopolymer of thymidine occurred on both the alpha M and beta 2 subunits. Soluble fibrinogen, a natural ligand for Mac-1, was an ex cellent competitor of the binding of a phosphorothioate oligodeoxynucl eotide to both TNF-alpha-activated and nonactivated PMNs. Upregulation of cell-surface Mac-1 expression increased cell-surface binding of ol igodeoxynucleotides. Binding was inhibited by anti-Mac-1 monoclonal an tibodies, and the increase in cell-surface binding was correlated with a three- to fourfold increase in internalization by PMNs. An oligodeo xynucleotide inhibited beta 2-dependent migration through Matrigel, bu t the production of reactive oxygen species in PMNs adherent to fibrin ogen dramatically increased. Thus, our data demonstrate that Mac-1 is a cell-surface receptor for oligodeoxynucleotides that can mediate the ir internalization and that this binding may have important functional consequences.