Pentraxins at the Crossroads Between Innate Immunity, Inflammation, Matrix Deposition, and Female Fertility

Abstract

C reactive protein, the first innate immunity receptor identified, and serum amyloid P component are classic short pentraxins produced in the liver. Long pentraxins, including the prototype PTX3, are expressed in a variety of tissues. Some long pentraxins are expressed in the brain and some are involved in neuronal plasticity and degeneration. PTX3 is produced by a variety of cells and tissues, most notably dendritic cells and macrophages, in response to Toll-like receptor (TLR) engagement and inflammatory cytokines. PTX3 acts as a functional ancestor of antibodies, recognizing microbes, activating complement, and facilitating pathogen recognition by phagocytes, hence playing a nonredundant role in resistance against selected pathogens. In addition, PTX3 is essential in female fertility because it acts as a nodal point for the assembly of the cumulus oophorus hyaluronan-rich extracellular matrix. Thus, the prototypic long pentraxin PTX3 is a multifunctional soluble pattern recognition receptor at the crossroads between innate immunity, inflammation, matrix deposition, and female fertility.

DC-SIGN (CD209), pentraxin 3 and vitamin D receptor gene variants associate with pulmonary tuberculosis risk in West Africans

“…6 Although the PTX3 relevance to TB pathogenesis has not yet been determined, its role in innate immunity, the interaction with mycobacterial wall molecules 7,8 and the apparent correlation of expression with disease activity 9 make it an attractive candidate for studies on genetic susceptibility to TB.…”

C-reactive protein functions as a negative regulator of macrophage activation induced by apoptotic DNA

“…CRP binds to apopDNA and promotes macrophage-mediated apopDNA uptake Accumulating data indicate that CRP has the capacity of binding to nuclear antigen (Garlanda et al, 2005;Bottazzi et al, 2010). To assess the binding ability of CRP to apopDNA, we performed dot blot analysis and found that CRP could bind to apopDNA (Fig.…”

“…*** p < 0.001. rabbit CRP transgenic mice (Xia and Samols, 1997). Because of low levels of CRP ( < 5 μg/mL) in mice, the murine model was shown to be useful to test the activity of transgenic or supplemental CRP in vitro and in vivo (Garlanda et al, 2005). Human and rabbit CRP could activate mouse complement and bind to Fcγ receptors on mouse macrophages (Rodriguez et al, 2007), so we chose human CRP to investigate its roles in modulating macrophage activation.…”

“…More recently, C-reactive protein (CRP), a member of the pentraxin family with an ability to bind to nuclear antigens as well as to damaged membranes and microbial antigens (Du Clos, 1989), was found to play a key role in the protection from autoimmune disease (Ogden and Elkon, 2005;Rodriguez et al, 2005;. Moreover, CRP was a prototypic acute phase protein produced mainly in response to inflammation, infection, or tissue damage (Garlanda et al, 2005;Bottazzi et al, 2010) and was reported to recognize nuclear autoantigens released from apoptotic cells, opsonize them through interacting with cell-surface FcγR, thereby activating macrophage-mediated phagocytosis (Mold et al, 2001;Bottazzi et al, 2010). In addition to activating phagocytosis through FcγR, emerging evidence demonstrated that CRP could also regulate immune responses (Marjon et al, 2009), indicating that CRP could modulate nuclear antigen-mediated immune response.…”

Serum amyloid P component facilitates DNA clearance and inhibits plasmid transfection: implications for human DNA vaccine

“…20 Furthermore, hSAP is constitutively present in human serum at 20-40 mg ml À1 and is a normal component of basement membrane. 21 Most importantly, several reports have shown that SAP strongly binds to CD14 + monocytes 22 and opsonizes its ligands in an Fc receptor-dependent manner. [23][24][25][26] In this regard, hSAP has been considered a candidate DNA vaccine 'scavenger' that requires further investigation.…”