Suppression by human recombinant gamma interferon of in vitro macrophage nonopsonic and opsonic phagocytosis and killing.
Although gamma interferon (IFN-gamma) exerts profound effects on the state of activation of macrophages, its influence on receptor-mediated phagocytosis and killing of extracellular bacteria is poorly understood. Human monocytes cultured in the presence of human recombinant IFN-gamma exhibited an enhanced capacity to produce superoxide anion. Although these cells bound greater numbers of particles via Fc receptors, their capacity to phagocytose by these receptors or to bind or ingest particles via receptors for C3bi, mannose, or unopsonized Pseudomonas aeruginosa was substantially depressed in a dose-dependent fashion (0.1 to 1,000 U of IFN-gamma per ml). Macrophage phagocytosis of P. aeruginosa and Staphylococcus aureus opsonized with whole serum or with serum deficient in immunoglobulin or complement was also depressed. Macrophages cultured in the presence of IFN-gamma had a diminished capacity to kill both unopsonized and opsonized P. aeruginosa. We conclude that IFN-gamma inhibits macrophage nonopsonic and opsonic receptor-mediated phagocytosis and killing but enhances oxidative radical generation; its production may exacerbate host tissue damage during chronic infection with extracellular pathogens.
Speert
D P
DP
Division of Infectious and Immunological Diseases, British Columbia's Children's Hospital, Vancouver, Canada.
Thorson
L
L
D002478:Cells, Cultured; D006801:Humans; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism / Q000502:physiology*; D009895:Opsonin Proteins / Q000378:metabolism / Q000502:physiology*; D010587:Phagocytosis / Q000187:drug effects*; D011550:Pseudomonas aeruginosa / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D011994:Recombinant Proteins; D013211:Staphylococcus aureus / Q000254:growth & development / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D009895:Opsonin Proteins; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; C028495:phagocytosis receptor; D013481:Superoxides; D007371:Interferon-gamma