C1q and Mannose Binding Lectin Engagement of Cell Surface Calreticulin and Cd91 Initiates Macropinocytosis and Uptake of Apoptotic Cells

By C. A. Ogden, A. deCathelineau, P. Hoffmann, D. Bratton, B. Ghebrehiwet, Valerie Fadok, P. Henson. Journal of Experimental Medicine, 2001

1,250 citations recorded by the source corpus.

Removal of apoptotic cells is essential for maintenance of tissue homeostasis, organogenesis, remodeling, development, and maintenance of the immune system, protection against neoplasia, and resolution of inflammation. The mechanisms of this removal involve recognition of the apoptotic cell surface and initiation of phagocytic uptake into a variety of cell types. Here we provide evidence that C1q and mannose binding lectin (MBL), a member of the collectin family of proteins, bind to apoptotic cells and stimulate ingestion of these by ligation on the phagocyte surface of the multifunctional protein, calreticulin (also known as the cC1qR), which in turn is bound to the endocytic receptor protein CD91, also known as the α-2-macroglobulin receptor. Use of these proteins provides another example of apoptotic cell clearance mediated by pattern recognition molecules of the innate immune system. Ingestion of the apoptotic cells through calreticulin/CD91 stimulation is further shown to involve the process of macropinocytosis, implicated as a primitive and relatively nonselective uptake mechanism for C1q- and MBL-enhanced engulfment of whole, intact apoptotic cells, as well as cell debris and foreign organisms to which these molecules may bind.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/12a63961aa097ffd344203807144a306f361402b

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In Immunology

1. Guido Kroemer
2. L. Zitvogel
3. Irving L. Weissman
4. R. Majeti
5. H. Hemmi
6. K. Ravichandran
7. U. Lorenz
8. M. Chao

Citations in the corpus

• Complement System Part II: Role in Immunity (2015, background): “Similar functions are described for mannose binding lectin (MBL), one of the recognition molecules of the LP (14).”
• Cell-surface calreticulin initiates clearance of viable or apoptotic cells through trans-activation of LRP on the phagocyte. (2005, neutral): “Receptor-associated protein (RAP) has been used extensively as an antagonist in the study of LRP and blocks LRP signaling to a large variety of ligands (Bu, 2001; Obermoeller-McCormick et al., 2001; Orr et al., 2003a).”
• Tumor microenvironment complexity and therapeutic implications at a glance (2020, background): “Nuclear fragments that are not engulfed by apoptotic bodies act as self-antigen and are the source of the autoimmune system-related diseases, e.g. systemic lupus erythematosus [218] [219] [220] .”
• Apoptosis: controlled demolition at the cellular level (2008, background): “Furthermore, the ability of macrophage lectins, such as mannose-binding lectin and lung surfactant proteins A and D, to act as receptors for apoptotic cells indicates the existence of carbohydrate signal”
• Calreticulin exposure dictates the immunogenicity of cancer cell death (2007, background): “CRT on dying tumor cells is required for phagocytosis by DC In view of the established role of CRT as an 'eat me' signa”
• The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors (2012, background): “Several prophagocytic signals have been identified, including cell surface calreticulin and phosphatidylserine (34, 35).”