Killing of Borrelia burgdorferi by macrophages is dependent on oxygen radicals and nitric oxide and can be enhanced by antibodies to outer surface proteins of the spirochete.
Interaction of B. burgdorferi organisms with mouse bone marrow-derived macrophages (BMM phi) leads to phagocytosis of microorganisms, induction of nitric oxide (NO) and superoxide radicals (O2-) by BMM phi and killing of spirochetes. Destruction of spirochetes by BMM phi was quantified by a new method based on the release of radioactivity from spirochetes pre-labelled with [3H]adenine. Uptake of B. burgdorferi by BMM phi, which mainly occurs by coiling phagocytosis, generation of NO and O2- radicals as well as killing of spirochetes were significantly enhanced by pre-opsonization of spirochetes with monoclonal antibodies (mAb) to the outer surface proteins A and B but not with those to the periplasmic flagellin. Addition of inhibitors specific for NO and O2- radical synthesis either separately or together to cultures of BMM phi and spirochetes resulted in only partial reduction of the killing potential of effector cells. The data indicate that NO and O2- radicals are necessary, but not sufficient, for complete elimination of B. burgdorferi by macrophages. Together with previous findings that protection against B. burgdorferi infection is conveyed by humoral immune responses the present data indicate that one of the important functions of specific antibodies is their participation in macrophage-mediated control of spirochetes.
Modolell
M
M
Max-Planck-Institut für Immunbiologie, Freiburg, Germany.
Schaible
U E
UE
Rittig
M
M
Simon
M M
MM
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D001428:Bacterial Vaccines; D001854:Bone Marrow Cells; D015748:Borrelia burgdorferi Group / Q000276:immunology* / Q000648:ultrastructure; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D005260:Female; D008074:Lipoproteins; D008193:Lyme Disease / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000648:ultrastructure; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D010587:Phagocytosis; D013481:Superoxides / Q000378:metabolism*
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D008074:Lipoproteins; C072045:OspA protein; D013481:Superoxides; D009569:Nitric Oxide