Abstract
We have previously reported that apolipoprotein E (apoE), a protein component of very-low-density lipoproteins (VLDL) and high-density lipoproteins and a potent plasma-borne atheroprotective factor, exerts anti-inflammatory activity in macrophages by switching the activation profile from M1 (“classic”) to M2 (“alternative”) in a process involving signaling via low-density lipoprotein receptor (LDLR) family members including the VLDL receptor (VLDLR) or apoE receptor-2 (apoER2). The present study was undertaken to investigate whether LDLR-related protein 1 (LRP-1), another member of the LDLR family and a ubiquitously expressed multifunctional cell surface receptor, modulates M1→M2 conversion in murine macrophages. We investigate bone marrow or peritoneal macrophages isolated from wild-type C57/Bl6 mice or mice with conditional inactivation of the LRP-1 gene in the myeloid lineage for the expression of polarization markers. Our results suggest that the deficiency of LRP-1 down-regulates M2 marker expression in macrophages, while enhancing the macrophage response to M1 stimuli. To our knowledge, this is the first demonstration that LRP-1 affects macrophage polarization and promotes the development of an anti-inflammatory M2 functional phenotype.
References
Baitsch D, Bock HH, Engel T, Telgmann R, Müller-Tidow C, Varga G, Bot M, Herz J, Robenek H, von Eckardstein A, Nofer JR (2011) Apolipoprotein E induces antiinflammatory phenotype in macrophages. Arterioscler Thromb Vasc Biol 31:1160–1168
Boucher P, Gotthardt M, Li WP, Anderson RG, Herz J (2003) LRP: role in vascular wall integrity and protection from atherosclerosis. Science 300:329–332
Hoeksema MA, Stöger JL, de Winther MP (2012) Molecular pathways regulating macrophage polarization: implications for atherosclerosis. Curr Atheroscler Rep 14:254–263
Llorente-Cortés V, Martínez-González J, Badimon L (2000) LDL receptor-related protein mediates uptake of aggregated LDL in human vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 20:1572–1579
Llorente-Cortés V, Royo T, Otero-Viñas M, Berrozpe M, Badimon L (2007) Sterol regulatory element binding proteins downregulate LDL receptor-related protein (LRP1) expression and LRP1-mediated aggregated LDL uptake by human macrophages. Cardiovasc Res 74:526–536
May P (2013) The low-density lipoprotein receptor-related protein 1 in inflammation. Curr Opin Lipidol 24:134–137
May P, Herz J, Bock HH (2005) Molecular mechanisms of lipoprotein receptor signalling. Cell Mol Life Sci 62:2325–2338
Overton CD, Yancey PG, Major AS, Linton MF, Fazio S (2007) Deletion of macrophage LDL receptor-related protein increases atherogenesis in the mouse. Circ Res 100:670–677
Rohlmann A, Gotthardt M, Hammer RE, Herz J (1998) Inducible inactivation of hepatic LRP gene by cre-mediated recombination confirms role of LRP in clearance of chylomicron remnants. J Clin Invest 101:689–695
Yancey PG, Blakemore J, Ding L, Fan D, Overton CD, Zhang Y, Linton MF, Fazio S (2010) Macrophage LRP-1 controls plaque cellularity by regulating efferocytosis and Akt activation. Arterioscler Thromb Vasc Biol 30:787–795
Yancey PG, Ding Y, Fan D, Blakemore JL, Zhang Y, Ding L, Zhang J, Linton MF, Fazio S (2011) Low-density lipoprotein receptor-related protein 1 prevents early atherosclerosis by limiting lesional apoptosis and inflammatory Ly-6Chigh monocytosis: evidence that the effects are not apolipoprotein E dependent. Circulation 124:454–464
Zurhove K, Nakajima C, Herz J, Bock HH, May P (2008) Gamma-secretase limits the inflammatory response through the processing of LRP1. Sci Signal 1:ra15
Acknowledgments
The help of Dr. Kai Zurhove and Beate Schulte is gratefully acknowledged.
Author information
Authors and Affiliations
Corresponding author
Additional information
Petra May and Hans H. Bock contributed equally to this work.
This work was funded by the Deutsche Forschungsgemeinschaft (DFG; MA2410/1-2-4, to P.M.), Bundesministerium für Bildung und Forschung (BMBF; e:bio ReelinSys, to H.B.) and intramural resources of the Center for Laboratory Medicine (to J.-R.N.).
Rights and permissions
About this article
Cite this article
May, P., Bock, H.H. & Nofer, JR. Low density receptor-related protein 1 (LRP1) promotes anti-inflammatory phenotype in murine macrophages. Cell Tissue Res 354, 887–889 (2013). https://doi.org/10.1007/s00441-013-1699-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00441-013-1699-2