Distribution of the Alpha 2-macroglobulin Receptor/low Density Lipoprotein Receptor-related Protein in Human Tissues

Overview

Journal Cell Tissue Res

Specialties Anatomy & Histology
Cell Biology

Date 1992 Sep 1

PMID 1423505

Citations 94

Authors

S K Moestrup

J GLIEMANN

G Pallesen

Affiliations

Soon will be listed here.

Abstract

The hepatic alpha 2-macroglobulin receptor (alpha 2MR)/low density lipoprotein receptor-related protein (LRP) binds and endocytoses alpha 2-macroglobulin-proteinase complexes in plasma. In addition, it binds lipoproteins, a novel 40 kDa protein, and complexes between plasminogen activators and plasminogen activator inhibitor type-1. This study shows, for the first time, the tissue distribution of alpha 2MR/LRP as determined by immunohistochemistry with specific monoclonal antibodies. The analysis revealed alpha 2MR/LRP-expression in a restricted spectrum of cell types, including neurons and astrocytes in the central nervous system, epithelial cells of the gastrointestinal tract, smooth muscle cells, fibroblasts, Leydig cells in testis, granulosa cells in ovary, and dendritic interstitial cells of kidney. Monocyte-derived cells displayed marked alpha 2MR/LRP expression in the phagocytes of liver, lung and lymphoid tissues, but no or low expression in antigen-presenting cells including Langerhans' cells of the skin. The high abundance of alpha 2MR/LRP in certain cell types of most organs suggests two main routes for alpha 2MR/LRP-mediated ligand clearance: (1) systemic removal in liver of circulating ligands, and (2) non-hepatic interstitial removal in different organs, including the brain.

Citing Articles

Lipidopathy disrupts peripheral and central amyloid clearance in Alzheimer's disease: Where are our knowledge.

Darabi S, Charkhat Gorgich E, Moradi F, Rustamzadeh A IBRO Neurosci Rep. 2025; 18:191-199.

PMID: 39906286 PMC: 11791331. DOI: 10.1016/j.ibneur.2025.01.004.

Skeletal progenitor LRP1 deficiency causes severe and persistent skeletal defects with Wnt pathway dysregulation.

Alhashmi M, Gremida A, Maharana S, Antonaci M, Kerr A, Fu S Bone Res. 2025; 13(1):17.

PMID: 39865089 PMC: 11770177. DOI: 10.1038/s41413-024-00393-x.

The Low-Density Lipoprotein Receptor-Related Protein-1 Is Essential for Dengue Virus Infection.

Huerta V, Martin A, Sarria M, Guirola O, Yero A, Ramos Y Viruses. 2024; 16(11).

PMID: 39599807 PMC: 11599027. DOI: 10.3390/v16111692.

Advances in Intrathecal Nanoparticle Delivery: Targeting the Blood-Cerebrospinal Fluid Barrier for Enhanced CNS Drug Delivery.

Madadi A, Sohn M Pharmaceuticals (Basel). 2024; 17(8).

PMID: 39204177 PMC: 11357388. DOI: 10.3390/ph17081070.

Low-Density Lipoprotein Receptor-Related Protein 1 as a Potential Therapeutic Target in Alzheimer's Disease.

Petralla S, Panayotova M, Franchina E, Fricker G, Puris E Pharmaceutics. 2024; 16(7).

PMID: 39065645 PMC: 11279518. DOI: 10.3390/pharmaceutics16070948.

References

Van Leuven F, Cassiman J, Van Den Berghe H . Demonstration of an alpha2-macroglobulin receptor in human fibroblasts, absent in tumor-derived cell lines. J Biol Chem. 1979; 254(12):5155-60. View

Pietromonaco S, Kerjaschki D, Binder S, Ullrich R, Farquhar M . Molecular cloning of a cDNA encoding a major pathogenic domain of the Heymann nephritis antigen gp330. Proc Natl Acad Sci U S A. 1990; 87(5):1811-5. PMC: 53573. DOI: 10.1073/pnas.87.5.1811. View

Cheng C, Grima J, Stahler M, Guglielmotti A, Silvestrini B, Bardin C . Sertoli cell synthesizes and secretes a protease inhibitor, alpha 2-macroglobulin. Biochemistry. 1990; 29(4):1063-8. DOI: 10.1021/bi00456a031. View

Haye K, FOSTER R, Goff J, Kaufman S . Endocytosis of alpha 2-macroglobulin is developmentally regulated during myogenesis. Dev Biol. 1986; 114(2):470-4. DOI: 10.1016/0012-1606(86)90211-3. View

Shi D, Savona C, Gagnon J, Cochet C, Chambaz E, Feige J . Transforming growth factor-beta stimulates the expression of alpha 2-macroglobulin by cultured bovine adrenocortical cells. J Biol Chem. 1990; 265(5):2881-7. View

Monard D . Cell-derived proteases and protease inhibitors as regulators of neurite outgrowth. Trends Neurosci. 1988; 11(12):541-4. DOI: 10.1016/0166-2236(88)90182-8. View

Bauer J, Strauss S, Ganter U, Schlegel P, Witt I, Yolk B . Interleukin-6 and alpha-2-macroglobulin indicate an acute-phase state in Alzheimer's disease cortices. FEBS Lett. 1991; 285(1):111-4. DOI: 10.1016/0014-5793(91)80737-n. View

Davidsen O, Christensen E, GLIEMANN J . The plasma clearance of human alpha 2-macroglobulin-trypsin complex in the rat is mainly accounted for by uptake into hepatocytes. Biochim Biophys Acta. 1985; 846(1):85-92. DOI: 10.1016/0167-4889(85)90113-2. View

Herz J, Goldstein J, Strickland D, Ho Y, Brown M . 39-kDa protein modulates binding of ligands to low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor. J Biol Chem. 1991; 266(31):21232-8. View

10.

Kristensen T, Moestrup S, GLIEMANN J, Bendtsen L, Sand O, Sottrup-Jensen L . Evidence that the newly cloned low-density-lipoprotein receptor related protein (LRP) is the alpha 2-macroglobulin receptor. FEBS Lett. 1990; 276(1-2):151-5. DOI: 10.1016/0014-5793(90)80530-v. View

11.

Kaplan J, Nielsen M . Analysis of macrophage surface receptors. I. Binding of alpha-macroglobulin . protease complexes to rabbit alveolar macrophages. J Biol Chem. 1979; 254(15):7323-8. View

12.

GLIEMANN J, Davidsen O . Characterization of receptors for alpha 2-macroglobulin-trypsin complex in rat hepatocytes. Biochim Biophys Acta. 1986; 885(1):49-57. DOI: 10.1016/0167-4889(86)90037-6. View

13.

Strickland D, Ashcom J, Williams S, Battey F, Behre E, McTigue K . Primary structure of alpha 2-macroglobulin receptor-associated protein. Human homologue of a Heymann nephritis antigen. J Biol Chem. 1991; 266(20):13364-9. View

14.

Nykjaer A, Petersen C, Moller B, Jensen P, Moestrup S, Holtet T . Purified alpha 2-macroglobulin receptor/LDL receptor-related protein binds urokinase.plasminogen activator inhibitor type-1 complex. Evidence that the alpha 2-macroglobulin receptor mediates cellular degradation of urokinase receptor-bound complexes. J Biol Chem. 1992; 267(21):14543-6. View

15.

Munck Petersen C, Ejlersen E, Wendelboe Hansen P, GLIEMANN J . Binding of alpha-2-macroglobulin trypsin complex to human monocytes in culture. Scand J Clin Lab Invest. 1987; 47(1):55-61. View

16.

Pallesen G, Beverley P, Lane E, Madsen M, Mason D, STEIN H . Nature of non-B, non-T lymphomas: an immunohistological study on frozen tissues using monoclonal antibodies. J Clin Pathol. 1984; 37(8):911-8. PMC: 498891. DOI: 10.1136/jcp.37.8.911. View

17.

Kowal R, Herz J, Goldstein J, ESSER V, Brown M . Low density lipoprotein receptor-related protein mediates uptake of cholesteryl esters derived from apoprotein E-enriched lipoproteins. Proc Natl Acad Sci U S A. 1989; 86(15):5810-4. PMC: 297720. DOI: 10.1073/pnas.86.15.5810. View

18.

van Dijk M, Ziere G, Boers W, Linthorst C, Bijsterbosch M, Van Berkel T . Recognition of chylomicron remnants and beta-migrating very-low-density lipoproteins by the remnant receptor of parenchymal liver cells is distinct from the liver alpha 2-macroglobulin-recognition site. Biochem J. 1991; 279 ( Pt 3):863-70. PMC: 1151526. DOI: 10.1042/bj2790863. View

19.

Christensen E, GLIEMANN J, Moestrup S . Renal tubule gp330 is a calcium binding receptor for endocytic uptake of protein. J Histochem Cytochem. 1992; 40(10):1481-90. DOI: 10.1177/40.10.1382088. View

20.

Cordell J, Falini B, Erber W, Ghosh A, Abdulaziz Z, MacDonald S . Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem. 1984; 32(2):219-29. DOI: 10.1177/32.2.6198355. View