Mac-1 (CD11b/CD18) is an oligodeoxynucleotide-binding protein

We have studied the interactions of phosphodiester and phosphorothioate oligodeoxynucleotides with Mac-1 (CD11b/CD18; M2), a heparin-binding integrin found predominately on the surface of polymorphonuciear leukocytes (PMNs), macrophages and natural killer cells. Binding of a homopolymer of thymidine occurred on both the M and 2 subunits. Soluble fibrinogen, a natural figand for Mac-1, was an excellent competitor of the binding of a phosphorothioate oligodeoxynucleotide to both TNF--activated and nonactivated PMNs. Upregulation of cell-surface Mac-1 expression increased cell-surface binding of oligodeoxynucleotides. Binding was inhibited by anti-Mac-1 monoclonal antibodies, and the increase in cell-surface binding was correlated with a three- to fourfold increase in internalization by PMNs. An oligodeoxynucleotide inhibited 2-dependent migration through Matrigel, but the production of reactive oxygen species in PMNs adherent to fibrinogen dramatically increased. Thus, our data demonstrate that Mac-1 is a cell-surface receptor for oligodeoxynucleotides that can medi ate their internalization and that this binding may have important functional consequences.

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