C-Reactive Protein Binds to Apoptotic Cells, Protects the Cells from Assembly of the Terminal Complement Components, and Sustains an Antiinflammatory Innate Immune Response

By Debra Gershov, Sunjung Kim, N. Brot, K. Elkon. Journal of Experimental Medicine, 2000

678 citations recorded by the source corpus.

C-reactive protein (CRP) is a serum protein that is massively induced as part of the innate immune response to infection and tissue injury. As CRP has been detected in damaged tissues and is known to activate complement, we assessed whether apoptotic lymphocytes bound CRP and determined the effect of binding on innate immunity. CRP bound to apoptotic cells in a Ca2+-dependent manner and augmented the classical pathway of complement activation but protected the cells from assembly of the terminal complement components. Furthermore, CRP enhanced opsonization and phagocytosis of apoptotic cells by macrophages associated with the expression of the antiinflammatory cytokine transforming growth factor β. The antiinflammatory effects of CRP required C1q and factor H and were not effective once cells had become necrotic. These observations demonstrate that CRP and the classical complement components act in concert to promote noninflammatory clearance of apoptotic cells and may help to explain how deficiencies of the classical pathway and certain pentraxins lead to impaired handling of apoptotic cells and increased necrosis with the likelihood of immune response to self.

Subfields: Immunology, Physiology, Surgery

View Paper: https://www.semanticscholar.org/paper/38642023d506b1b9420d12459464dab1bfc393fe

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Citations in the corpus

• Innate and acquired immunity in atherogenesis (2002, background): “CRP binds to apoptotic cells as well, although the identity of the ligand involved has not been determine”
• Complement - a key system for immune surveillance and homeostasis (2010, background): “Early stage effectors are preferentially used because the modified apoptotic cell surface acquires CRP and C1q together with f”
• Hydrophobicity: an ancient damage-associated molecular pattern that initiates innate immune responses (2004, background): “C-reactive protein binds damaged membranes and can facilitate opsonophagocytosis of pathogens and of necrotic-cell debri”
• The role of defective clearance of apoptotic cells in systemic autoimmunity (2010, background): “CRP binds to the membranes of damaged cells, to phospholipids and to small nuclear ribonucleoproteins”
• Complement regulators and inhibitory proteins (2009, background): “This initiates early steps of the classical pathway but blocks the formation and amplification of the C5 convertas”
• The Pivotal Role of the Complement System in Aging and Age-related Macular Degeneration: Hypothesis Re-visited (2009, neutral): “DNA samples derived from 1162 total case and control subjects were used for genotyping all complement gene-associated SNPs identified in the SNP discovery phase, as well as additional SNPs chosen from public databases.”