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.