Disease relevance of PTX3

• We found an intense staining for PTX3 in the expanded mesangial areas of renal biopsies obtained from patients with IgA glomerulonephritis [1].
• Overexpression of PTX3 worsens acute lung injury [2].
• Scattered PTX3-positive cells were also detected in glomeruli of type I membranoproliferative glomerulonephritis [1].
• Whole mycobacteria (Mycobacterium bovis BCG) strongly induced PTX3 expression [3].
• PTX3 in small-vessel vasculitides: an independent indicator of disease activity produced at sites of inflammation [4].

High impact information on PTX3

• 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 [5].
• 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 [5].
• 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 [5].
• 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 [5].
• The TLR2-activated functional program includes production of the long pentraxin PTX3, a soluble pattern recognition receptor involved in resistance against diverse pathogens [6].

Chemical compound and disease context of PTX3

• High-volume ventilation significantly enhanced PTX3 expression in the lung, either alone or in combination with LPS or hemorrhage [7].

Biological context of PTX3

• PTX3 is a prototypic long pentraxin that plays a non-redundant role in innate immunity against selected pathogens and in female fertility [8].
• Exogenous PTX3 restores a normal cumulus phenotype [8].
• Cytokine-induced gene expression at the crossroads of innate immunity, inflammation and fertility: TSG-6 and PTX3/TSG-14 [9].
• Both TSG-6 and PTX3 are synthesized in the ovary prior to ovulation, where they become components of an expanding viscoelastic matrix that surrounds the oocyte before its release from the follicle at the ovarian surface [9].
• PTX3 is a secreted multimeric glycoprotein which plays a key role in innate immunity by activating the classical complement pathway through specific recognition of the C1q subunit [10].

Anatomical context of PTX3

• Among leukocytes, only monocytes exposed to inflammatory cytokines or LPS expressed the PTX3 transcript, which was undetectable in resting or stimulated polymorphonuclear cells, T or B lymphocytes, and natural killer cells [11].
• PTX3 was recently cloned as an interleukin-1 (IL-1)-inducible gene in endothelial cells, with structural similarities to pentraxins in the C-terminal half of the molecule [11].
• PTX3 mRNA was also inducible in in vitro monocyte-derived macrophages, in tumor-associated macrophages, and in the myelomonocytic cell lines HL60, U937, and THP1, but not in GFD8, with the latter possibly representative of earlier stages of myelomonocytic differentiation [11].
• Inducible expression of PTX3, a new member of the pentraxin family, in human mononuclear phagocytes [11].
• The present study was designed to investigate the expression of PTX3 in the human leukocyte populations [11].

Associations of PTX3 with chemical compounds

• IL-4, but not dexamethasone or transforming growth factor-beta, inhibited PTX3 expression in monocytes [11].
• Pretreatment with either actinomycin D or cycloheximide abolished TNF-alpha-induced PTX3 expression, indicating the requirement for both transcriptional and translational regulation [2].
• Pretreatment with actinomycin D abolished LAM-induced PTX3 expression, whereas cycloheximide only partially reduced the expression [3].
• The NH2-terminal half of PTX3 shows no similarity to any known protein sequence and initiates with a putative signal peptide indicating that PTX3 is secreted [12].
• Unlike the classical pentraxins CRP and SAP, PTX3 did not bind phosphoethanolamine, phosphocholine, or high pyruvate agarose [13].
• Based on these findings, we conclude that estradiol and progesterone are involved in PTX3 induction and regulation during implantation [14].

Physical interactions of PTX3

• PTX3 binds FGF2 and inhibits its angiogenic activity on endothelial cells [15].

Regulatory relationships of PTX3

• Human peripheral blood mononuclear cells exposed to lipopolysaccharide (LPS) or IL-1 beta expressed significant levels of PTX3 mRNA [11].
• The importance of the JNK pathway for the regulated PTX3 expression may be a potential target for its regulation in the lung [2].
• In vitro, cultured human mesangial cells synthesized PTX3 when stimulated with TNF-alpha and IgA and exhibited specific binding for recombinant PTX3 [1].
• PTX3 protein secretion by activated monocytes is also suppressed by exposure to IFN-gamma [16].
• Human herpesvirus 8-derived viral IL-6 induces PTX3 expression in Kaposi's sarcoma cells [17].

Other interactions of PTX3

• Cycloheximide had no effect on PTX3 induction in U937 cells, but was inhibitory on monocytes exposed to LPS or IL-1 beta [11].
• TNFalpha-induced long pentraxin PTX3 expression in human lung epithelial cells via JNK [2].
• PTX3 is expressed in a variety of cell types, notably mononuclear phagocytes and endothelial cells, after exposure to the inflammatory cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) [3].
• Thus, PTX3, unlike the classical pentraxins CRP and SAP, is expressed and released by cells of the monocyte-macrophage lineage exposed to inflammatory signals [11].
• Female mice with a targeted disruption of either the TSG-6 or PTX3 gene show severe defects in fertility [9].

Analytical, diagnostic and therapeutic context of PTX3

• METHODS: Concentrations of PTX3, a pentraxin induced in endothelium by cytokines, were measured by enzyme-linked immunosorbent assay in the sera of 43 patients with Churg-Strauss syndrome, Wegener's granulomatosis, and microscopic polyangiitis [4].
• The PTX3 gene has been localized on human chromosome 3 band q25 by Southern blots of somatic cell hybrids and by in situ hybridization [12].
• While in gel filtration the protein is eluted with a molecular mass of congruent with900 kDa, gel electrophoresis using nondenaturing, nonreducing conditions revealed that PTX3 forms multimers predominantly of 440 kDa apparent molecular mass, corresponding to decamers, and that disulfide bonds are required for multimer formation [13].
• Expression of PTX3 by vIL-6-stimulated KS cell cultures was analysed by quantitative real-time reverse transcriptase-polymerase chain reaction [17].
• The joint fluid from RA patients contained higher levels of immunoreactive PTX3 than controls and the synovial tissue contained endothelial cells and synoviocytes positive for PTX3 by immunohistochemistry [18].

References