PTX3 is a member of the Pentraxin family of proteins which also includes CRP
Short and long pentraxins share a 200-amino-acid-long C-terminal domain that contains a motif known as the pentraxin signature (HxCxS/TWxS)
PTX3 is a “long penthraxin” and also has an unrelated N-terminal domain which mediates some of its binding activities (eg. Aspergillus)
acts as a bridge between the soluble and the cellular arms of innate immunity and its binding capabilities means it acts as a functional evolutionary predecessor of antibodies
it is involved in vascular inflammation and endothelial dysfunction through various mechanisms
it modulates inflammatory cells, thus stimulating vascular inflammation
PTX3 levels positively correlate with arterial hypertension, flow mediated dilation and, with intima media thickness.
circulating PTX3 level is a strong marker of disease severity in coronary artery disease and is predictive of cardiovascular and all-cause mortality independent of CRP
elevated serum or plasma levels of PTX3 are found in rheumatoid arthritis, small- and large-vessel vasculitides, other autoimmune diseases, infections, and degenerative disorders.
immune deposits of PTX3 have been found in the renal glomeruli and tubulointerstitial areas in lupus nephritis suggesting a pathophysiologic role in renal injury
appears to be protective against invasive aspergillosis
Physiology
production
rapidly produced at local sites of inflammation by macrophages, neutrophils, endothelial cells, dendritic cells, fibroblasts, and other cell types in response to IL-1 and TNF-α
in neutrophils, PTX3 is constitutively stored in the specific granules and is released by several stimuli, including TLR agonists
gene can be induced by the EGF-like factor AREG
polymorphisms in the PTX3 gene are associated with risk for pulmonary tuberculosis and P. aeruginosa infections in cystic fibrosis
actions
opsonisation actions by binding to:
selected fungi, bacteria, and viruses
several complement components (e.g., C1q and factor H) to help regulate complement activation
NB. all pentraxins are involved in complement regulation through interactions with C1q (CRP, SAP, PTX3), ficolins (CRP, PTX3), and factor H (CRP, PTX)
apoptotic cells
cell-adhesion molecules (P-selectin) and thus inhibit the rolling of leukocytes on the endothelium.
neutrophil-released PTX3 can regulate local inflammation by suppressing P-selectin-dependent recruitment of neutrophils to peripheral tissues
antiviral activity esp. for influenza and CMV
inhibition of virus-induced hemagglutination and viral neuramidase activity
neutralization of virus infectivity
within endothelial cells:
decreases nitric oxide (NO) synthesis
inhibits cell proliferation and alters their functions
blocks the effect of fibroblast growth factor 2 (FGF2) by making a molecular complex with these molecules inactivating them
interacting with P-selectin, it promotes vascular inflammatory response and endothelial dysfunction
increases the matrix metalloproteinases synthesis directly or by blocking NO synthesis
as an acute phase reactant in inflammation
developmental neural actions:
secreted by astrocytes mainly during late embryonic and early postnatal development
specifically enhances formation and function of developing excitatory synapses via the recruitment of AMPAR subunits
modulators
tumor necrosis factor-inducible gene 6 protein (TSG-6) block the PTX3-FGF2 interaction