C-reactive protein

C-reactive protein is an acute phase protein produced by the liver within 6 hours of an acute inflammatory stimulus. Levels peak after about 50 hours.

CRP is a pentraxin protein that exhibits calcium dependant ligand binding and a distinctive flattened β-jellyroll structure. (left - image - click to enlarge) CRP is so-named because it reacts with the somatic C polysaccharide of the bacterium Streptococcus pneumoniae. Serum amyloid P component is another pentraxin, acute phase protein.

CRP binds specifically to phosphocholine moieties, conferring a host-defensive role on CRP since phosphocholine is a component of microbial polysaccharides. CRP also binds to ligands exposed on damaged cells.

CRP-phosphocholine-binding:
● activates the classical complement pathway
● acts as an opsonin ligand for phagocytosis
● neutralizes the pro-inflammatory platelet-activating factor (PAF)
● down-regulates polymorphs
CRP
● increases production of tissue-factors by monocytes
● activates smooth muscle K+ ion channels (vasodilator)
● delays apoptosis of neutrophils when the pentameric structure is lost and the molecule exists as a monomer (mCRP)

CRP is mildly elevated in: systemic lupus erythematosus, systemic sclerosis, sermatomyositis, ulcerative colitis, leukaemia, and graft-versus-host disease (GVHD).

The C-reactive protein medical test measures levels of CRP to assess acute inflammation. An association has been demonstrated between sudden cardiac death, peripheral arterial disease and hs-CRP, so serum CRP levels may correlate with cardiovascular disease risk.

tags [Proteins] [C-reactive protein] [acute phase] [classical complement pathway] [inflammation] [pentraxin]

| 0 Guide-Glossary

mannose-binding protein

Mannose binding protein (MBP) or mannan-binding lectin (MBL) is a member of the collectin family, and is a C−type serum lectin that participates in the innate inflammatory response in defense against a variety of bacterial, fungal and viral pathogens.

▼ acute phase : CD45 : collectins : domains CRD vs CTLD vs CARD : evolution : ficolins : inflammatory response : lectin pathway of complement activation : MBL-MASP : mutations : receptor : T-cells ▼

MBP is an acute phase protein synthesized in response to pro-inflammatory cytokines early in the inflammatory response. The receptor that recognizes CRD-carrying MBP, and structurally-related complement or lectin opsonins (collectins), is widely distributed on leukocytes, platelets, and endothelial cells.

MBP initiates the lectin branch (MBL-MASP) of the complement cascade by binding to sugars on the surfaces of microorganisms, activating two MBP-associated serine proteases (MASP-1 and MASP-2). MBP is able to specifically recognize cell surface CD45 on immature, but not mature T cells.

The lectin pathway (MBL - MASP) is homologous to the classical pathway, but utilizes opsonin, mannan-binding lectin (MBL, MBP) and ficolins rather than C1q. Binding of mannan-binding lectin to mannose residues on the pathogen's surface activates the MBL-associated serine proteases, MASP-1, MASP-2, MASP-3, which cleave C4 into C4b and C2 into C2b. As in the classical pathway, C4b and C2b bind to form the C4b•C2b C3 convertase. Ficolins are homologous to MBL and function through MASPs. Diversified ficolins are of particular importance in invertebrates, which lack the adaptive immune response that evolved some 500 million years ago in jawed vertebrates. [] C-lectin phylogenetic tree, Immune branch, Snake toxins branch, Calcium-carbohydrate binding branch []

Mutations in the gene encoding mannose binding protein may result in defective opsonization. MBP is a 53 kDa homomultimeric trimer [] ribbon structure MBP [] Human mannose binding protein CRD [] space-fill structure hMBP [] superimposition of CRD/CTLD domains of mannose binding protein C (orange), IX/X binding protein (red), lithostathine (green), human CD94 (purple) []

MBP carries the CRD domain, whose major function is calcium-dependent recognition of oligosaccharides at cell surfaces (carbohydrate-recognition domain (CRD not CARD, which is caspase recruitment domain). The C-type-lectin-like domain (CTLD) is located in a large variety of proteins and is similar to the CRD domain on C- lectins (C-lectin domain). Although CTLDs are similar to CRDs of C-lectins in sequence and structure, they serve different functions.

▲ф ф activation ф activation complement cascade : acute phase ф acute phase : CD45 : collectins ф complement system : domains CRD vs CTLD vs CARD : evolution »» Evolution : ficolins ф humoral immunity ф immune cytokines ф immune response ф inflammatory response : inflammatory response : lectin pathway of complement activation : MBL-MASP : mutations »» Mutation ф pathogens : receptor ф receptors : T-cells ф T cells ▲ф

▲ Top ▲

tags [Proteins] [mannose-binding proteins] [acute phase] [C-lectins] [collectins]

| 0 Guide-Glossary