Clearance of neutrophil-derived myeloperoxidase by the macrophage mannose receptor.
Uptake of neutrophil-derived myeloperoxidase by the macrophage mannose receptor was studied. Rat bone marrow-derived macrophages internalized 75% of [125I]myeloperoxidase through a mannose-specific process. Uptake via the mannose receptor is highly sensitive to treatment with oxidants. Treatment of rat macrophages with 1 mM H2O2 for 30 min resulted in a 94% reduction in uptake of myeloperoxidase. By Percoll gradient fractionation studies, 38% of internalized myeloperoxidase was delivered to the lysosomal compartment during a 15-min chase period, similar to findings for delivery of other ligands for this receptor. Once in the lysosome, the myeloperoxidase remained enzymatically active for several hours, with 50% activity remaining at 8 h. Finally, myeloperoxidase-containing macrophages had an increased capacity to down-regulate their own mannose receptors or receptors on neighboring macrophages, possibly through the myeloperoxidase-mediated production of oxidized halogens. Thus, the macrophage mannose receptor plays a potentially physiologic role in regulating extracellular myeloperoxidase levels. The receptor-mediated uptake may either arm the macrophage to contribute to oxidant-mediated tissue damage or may function to clear extracellular myeloperoxidase during the resolution phase of the inflammatory process.
Shepherd
V L
VL
Veterans Administration Medical Center, Memphis, Tennessee.
Hoidal
J R
JR
D000818:Animals; D001854:Bone Marrow Cells; D015536:Down-Regulation; D004705:Endocytosis; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D037181:Lectins, C-Type; D008247:Lysosomes / Q000201:enzymology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D009504:Neutrophils / Q000201:enzymology*; D009195:Peroxidase / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic / Q000378:metabolism*
D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D006861:Hydrogen Peroxide; D009195:Peroxidase; D005966:Glucuronidase