PTX3

PTX3
Properties of human protein
Mass / length primary structure	364 amino acids
Secondary to quaternary structure	Homoctamer
Cofactor	C1q
Identifier
Gene names	PTX3 ; TNFAIP5; TSG-14
External IDs	OMIM : 602492 ; UniProt : P26022 ;
Occurrence
Homology family	Pentaxine
Parent taxon	Euteleostomi
	Orthologue

PTX3 is a soluble receptor that plays an important role in the immune system . He is a member of the Pentraxine family and belongs to the group of Pattern Recognition Receptors (PRRs). These receptors can recognize certain patterns or structures of antigens . These patterns are also known as pathogen-associated molecular patterns (PAMPs). The pattern recognition receptors, including the PTX3 receptor, are part of the innate immune system . The development of an immune response by the adaptive or acquired immune system , on the other hand, is rather inhibited.

The PTX3 receptor circulates freely in the blood until it encounters an antigen with a certain suitable pathogen-associated molecular pattern. By binding the receptor, the complement system, also part of the innate immune system, is activated. The antigen in question is marked as “foreign” (so-called opsonization ) and removed from neutrophils by phagocytosis . In addition, the PTX3 receptor also contributes to the elimination of the body's own components, for example dead cells as a result of apoptosis ( programmed cell death ).

Molecular structure

Pentamer or 10- and 20-mer; Protomer 381 AS, about 40 kDa without glycosylation
178 aa N-terminal domain with no homology to other proteins
203 AS C-terminal domain similar to the short Pentraxine C-reactive protein (CRP) and serum amyloid P (SAP)
Asn-220 carries a relevant N-glycosylation
Human chromosome 3q25
Promoter response elements : NF-κB , NFIL6, ETS1, AP1, SP1, PU1, PEA3

swell

The following types of cells form PTX3:

Cover tissue and glandular tissue (e.g. kidney tubules, alveolar epithelium, bronchial epithelium)
Endothelial cells
Smooth muscles , mesangial cells
Fibroblasts (cells in connective tissue )
Adipocytes (cells of adipose tissue )
myeloid dendritic cells
Monocytes , macrophages and foam cells
Precursors of the neutrophil granulocytes: promyelocytes , myelocytes , metamyelocytes
Neutrophil granulocytes contain PTX3 in secretion granules, but no longer have any mRNA .

Inducing substances

IL1beta, TNFalpha, LPS, Lipoarabinomannan, OmpA, oxLDL, cells in apoptosis
- via receptors for IL1, TNF and toll-like receptors
- these work via myd88 - NFKB stimulation and JNK
IL-10
IL-17
CD40L

Inhibiting substances

IL-4, IFN-gamma
PGE2
1,25-OH2-D3 vitamin
Dexamethasone
Statins (3HmgCoA reductase inhibitors)

Function as an immunoregulatory opsonin

Target antigen structures and cellular receptors for PTX3 are still largely unknown
The targets are own cells in apoptosis and various pathogens
C1q complement binding, activation of the classic complement path
Activation of defense cells, d. H. Neutrophil granulocytes
Reduced uptake of the antigen by dendrite cells, prevention of an adaptive immune reaction
Immune deviation towards Th-1

Relevant diseases

PTX3 seems to play a role in numerous diseases:

Aspergillus fumigatus : PTX3 is an essential opsonin here , it binds the conidia (galactomannan) so that they can be phagocytosed by the macrophages. Without PTX3, the Aspergillus fumigatus infection is fatal.
Influenza : Influenza hemagglutinin (with which the virus binds to the target cell) binds the sugar residue of the PTX-3, which makes it a so-called gamma inhibitor .
Some bacteria are recognized: Pseudomonas , Salmonella , Klebsiella (OmpA); Paracoccidioides
Vasculitis : The leukocytoclastic vasculitis is characterized by the fact that the perivascular remains of the decayed neutrophil granulocytes cannot be removed adequately by other phagocytes. PTX3 is produced in the active vasculitic lesion by endothelial cells (and certainly secreted by neutrophils). ANCA- positive cases of Wegener's granulomatosis and microscopic polyangiitis were investigated

IgA nephritis ( glomerulonephritis )

Scleroderma

Rheumatoid arthritis

Atherosclerosis : Expression in the macrophages / foam cells; Evidence in the subendothelium

Myocardial infarction : Both the PTX3 knockout as well as the PTX3 transgenic mouse show more pronounced tissue damage.

Systemic Inflammatory Response Syndrome (SIRS) and Sepsis

Chronic microinflammation: We see chronic monocytic activation with cytokine formation (IL1, IL6, TNF) in various underlying diseases:

Chronic kidney failure

Chronic heart failure ( positive predictive value for complications / clinical endpoints)

Systemic lupus erythematosus (SLE): less PTX3 is measured in the serum than in healthy subjects.

PTX3 as a biomarker

As an indicator of incipient infections, it reacts faster than the clinically used biomarker CRP.
Activity of some vasculitis
Early parameters unstable angina pectoris / myocardial infarction

Synonyms

Pentraxin 3, TSG-14, TNF stimulated gene 14.

Individual evidence

↑ M. Presta et al .: Role of the soluble pattern recognition receptor PTX3 in vascular biology. In: J Cell Mol Med. 11 (4), pp. 723-738 (1997) PMID 17760835

↑ Paramita Baruah et al: The tissue pentraxin PTX3 limits C1q-mediated complement activation and phagocytosis of apoptotic cells by dendritic cells. In: J Leukoc Biol 2006 Jul; 80 (1), pp. 87-95. Epub 2006 Apr 14 Full text (HTML) ( Memento of the original from September 6, 2008 in the Internet Archive ) Info: The archive link was inserted automatically and not yet checked. Please check the original and archive link according to the instructions and then remove this notice. Full text (PDF; 417 kB) ( Page no longer available , search in web archives ) Info: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice. PMID 16617159 @1@ 2 @1@ 2Template: Dead Link / www.jleukbio.org
↑ Xiaolin He et al .: Long pentraxin 3 in pulmonary infection and acute lung injury. In: Am J Physiol Lung Cell Mol Physiol. 2007 May; 292 (5), pp. L1039-1049. Epub 2007 Feb 2, full text (HTML) , PMID 17277044
↑ Benedetta Bussolati et al: The long pentraxin PTX3 is synthesized in IgA glomerulonephritis and activates mesangial cells. In: J Immunol. 2003 Feb 1; 170 (3), pp. 1466-1472. Full text (HTML) Full text (PDF; 747 kB) PMID 12538709

[PMID18598385-1] M. Presta et al .: Role of the soluble pattern recognition receptor PTX3 in vascular biology. In: J Cell Mol Med. 11 (4), pp. 723-738 (1997) PMID 17760835