Regulation of macrophage alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein by lipopolysaccharide and interferon-gamma.
alpha 2-Macroglobulin receptor/low density lipoprotein receptor-related protein (alpha 2M-R/LRP) is a broad specificity receptor that may function in lipoprotein metabolism, proteinase regulation, and growth factor regulation. In this study, we demonstrated that alpha 2M-R/LRP expression in macrophages can be markedly decreased by LPS and by IFN-gamma. Regulation of alpha 2M-R/LRP in RAW 264.7 cells was demonstrated at the mRNA, antigen, and receptor-function levels. In receptor-function studies, the decrease in alpha 2M-R/LRP expression was detected as a 90% decrease in the Bmax or maximum receptor binding capacity for activated alpha 2M after treatment with LPS or IFN-gamma. Western blot analysis of whole cell lysates demonstrated significant loss of alpha 2M-R/LRP heavy-chain. Northern blot analysis of poly(A)+ RNA revealed a marked decrease in alpha 2M-R/LRP mRNA after treatment with LPS (79% decrease) or IFN-gamma (70% decrease). Other cytokines, including tumor necrosis factor-alpha, transforming growth factor-beta-1, and interleukin-6 did not regulate alpha 2M-R/LRP. The ability of LPS and IFN-gamma to regulate alpha 2M-R/LRP was confirmed in experiments with primary cultures of murine bone marrow macrophages. These studies demonstrate that macrophage alpha 2M-R/LRP is subject to significant downregulation by physiologically significant cytokines and signaling macromolecules.
LaMarre
J
J
Department of Pathology, University of Virginia Health Sciences Center, Charlottesville 22908.
Wolf
B B
BB
Kittler
E L
EL
Quesenberry
P J
PJ
Gonias
S L
SL
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002460:Cell Line; D002478:Cells, Cultured; D004926:Escherichia coli; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D011061:Poly A / Q000235:genetics / Q000302:isolation & purification; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000187:drug effects / Q000378:metabolism*; D011973:Receptors, LDL / Q000187:drug effects / Q000378:metabolism*; D011994:Recombinant Proteins; D000511:alpha-Macroglobulins / Q000378:metabolism
D008070:Lipopolysaccharides; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D011973:Receptors, LDL; D011994:Recombinant Proteins; D000511:alpha-Macroglobulins; D011061:Poly A; D012313:RNA; D007371:Interferon-gamma