Pentraxins

Abstract

The pentraxin family of proteins is characterised by sequence and structural homology and calcium‐dependent ligand binding. The human pentraxins are C‐reactive protein (CRP) and serum amyloid P component (SAP), the former of which is a strong acute phase protein. The activities of CRP and SAP are mediated through the classical complement pathway and through activation of Fc receptors (FcRs). Pentraxins are pattern recognition molecules that play important roles in host defence and control of inflammation. Measurement of CRP in blood has been used to monitor inflammation and infection and more recently to predict cardiovascular disease. Recent studies suggest that each of the pentraxins plays a role in the regulation of inflammation and tissue fibrosis. Knockout and transgenic models suggest that these effects are due to interaction with FcRs on macrophages and dendritic cells. Ongoing laboratory studies and clinical trials suggest that pentraxins may have therapeutic benefits.

Key Concepts:

  • Pentraxins form a family of proteins based on structural homology and calcium‐dependent ligand binding.

  • Pentraxins are serum proteins that are important in host defence and regulation of the inflammatory response.

  • The functional activities of CRP and SAP are mediated by complement activation and by interaction with Fc receptors on leucocytes.

  • Structurally pentraxins are planar pentamers with five calcium‐dependent ligand‐binding sites on one face and a binding site for a single Fc receptor on the opposite face.

  • CRP and SAP are the two members of the pentraxin family found in most animals.

  • Human CRP is a strong acute phase reactant made in the liver in response to tissue injury or infection. CRP is often used to monitor inflammation or infection because of its rapid synthesis and clearance.

  • CRP has anti‐inflammatory activity mediated through Fcγ receptors in a number of mouse autoimmune models and in endotoxin shock.

  • SAP inhibits fibrocyte differentiation and prevents fibrosis in pulmonary and renal models.

  • Genetic polymorphisms in noncoding regions of the CRP gene determine baseline levels of CRP and are the risk factors for systemic lupus erythematosus, but not cardiovascular disease.

Keywords: acute phase protein; autoimmunity; complement; C‐reactive protein; Fc receptors; fibrocyte; inflammation; serum amyloid P component; systemic lupus erythematosus

Figure 1.

CRP binds to snRNP particles, the target of autoantibodies in systemic lupus erythematosus (SLE). Permeabilised Hep‐2 cells were stained with CRP and fluorescein isothiocyanate (FITC)‐conjugated anti‐CRP monoclonal antibody. The micrograph shows nuclear staining in a speckled pattern characteristic of snRNP. See, Du Clos .

Figure 2.

CRP structure. Left, Effector face of CRP that interacts with C1q and FcR; Right, Ligand binding site found on each subunit of the opposite face of CRP with Ca++ and PC in the binding pocket. See, Srinivasan et al. for a comparison of the CRP and SAP ligand binding sites.

Figure 3.

Pentraxin interaction with FcR by X‐ray crystallography. Top, the crystal structure of the SAP in complex with FcγRIIA 3D5O; Bottom, cartoon of the human FcγRs and FcαRI. See, Lu et al. and Nimmerjahn and Ravetch .

Figure 4.

Functional overview of interactions and proposed activities of pentraxins in the immune system.

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Mold, Carolyn, Sun, Peter D, and Du Clos, Terry W(Nov 2012) Pentraxins. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0024236]