The pentraxins are an ancient family of proteins with a unique architecture found as far back in evolution as the Horseshoe crab. In humans the two members of this family are C-reactive protein and serum amyloid P. Pentraxins are defined by their sequence homology, their pentameric structure and their calcium-dependent binding to their ligands. Pentraxins function as soluble pattern recognition molecules and one of the earliest and most important roles for these proteins is host defense primarily against pathogenic bacteria. They function as opsonins for pathogens through activation of the complement pathway and through binding to Fc gamma receptors. Pentraxins also recognize membrane phospholipids and nuclear components exposed on or released by damaged cells. CRP has a specific interaction with small nuclear ribonucleoproteins whereas SAP is a major recognition molecule for DNA, two nuclear autoantigens. Studies in autoimmune and inflammatory disease models suggest that pentraxins interact with macrophage Fc receptors to regulate the inflammatory response. Because CRP is a strong acute phase reactant it is widely used as a marker of inflammation and infection. 1. Introduction In this review, I focus on the two major, classical pentraxins: C-reactive protein (CRP) and serum amyloid P component (SAP). The pentraxins are serum proteins with a relatively uncommon pentameric structure. They function as pattern recognition molecules recognizing foreign antigens and altered self-antigens and tag these molecules for activation of the innate immune system. This property is characteristic of innate recognition molecules that preceded the development of the immunoglobulins. Pentraxins also interact with the complement system and Fc receptors to activate immune responses. It is likely that the interaction of pentraxins with the receptors for the Fc region of immunoglobulins preceded the development of immunoglobulins. 2. History The pentraxins appeared very early in evolution with several different forms present in the horseshoe crab, which has been referred to as a living fossil having persisted 250–300 million years [1]. Despite this long lineage, our understanding of the function of these proteins remained obscure until very recently. The discovery of CRP in man was achieved serendipitously in the blood of a patient with severe Streptococcus pneumoniae pneumonia. The protein appeared in the blood when the patient was systemically ill and was not detectable before the infection or after the infection had been eradicated [2]. These clinical investigators at the
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