Mac-1 (CD11b/CD18) is an oligodeoxynucleotide-binding protein.
We have studied the interactions of phosphodiester and phosphorothioate oligodeoxynucleotides with Mac-1 (CD11b/CD18; alpha M beta 2), a heparin-binding integrin found predominantly on the surface of polymorphonuclear leukocytes (PMNs), macrophages and natural killer cells. Binding 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 excellent competitor of the binding of a phosphorothioate oligodeoxynucleotide to both TNF-alpha-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 beta 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 mediate their internalization and that this binding may have important functional consequences.
Benimetskaya
L
L
Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA.
Loike
J D
JD
Khaled
Z
Z
Loike
G
G
Silverstein
S C
SC
Cao
L
L
el Khoury
J
J
Cai
T Q
TQ
Stein
C A
CA
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001667:Binding, Competitive; D018821:CD18 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D016177:Macrophage-1 Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008565:Membrane Proteins; D009504:Neutrophils / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D015398:Signal Transduction; D013873:Thionucleotides / Q000378:metabolism; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D004268:DNA-Binding Proteins; D008024:Ligands; D016177:Macrophage-1 Antigen; D008565:Membrane Proteins; D009838:Oligodeoxyribonucleotides; D017382:Reactive Oxygen Species; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D013873:Thionucleotides