Platelet Factor-4 (CXCL4)

About CXCL4 / PF4:

Platelet factor 4 (PF4) is a cytokine that belongs to the CXC chemokine family and is also known as a chemokine (C-X-C motif) and ligand 4 - CXCL4.

Chemokines are classified in four main subfamilies, these are CXC, CC, CX3C, and XC. Each of these proteins take their proteins from biological effects by interacting with g-protein linked transmembrane receptors known as chemokine receptors - these are found on the surface of target cells.

Chemokines are a group of small cytokines - signalling proteins that are secreted by the cells. The names of these cells come from their ability to induce directed chemotaxis in nearby cells that are responsive - these are called chemotactic cytokines. Cytokine proteins are classified as chemokines due to their behaviour and the structural characteristics that they hold. Also known for mediating chemotaxis, chemokines are around 8-10 kilodaltons in mass and usually have four cysteine residues kept in conserved locations, it’s these that allow them to form their three dimensional shape.

Many chemokines are pro-inflammatory and can be induced during an immune response to recruit cells of the immune system to the site of an infection. However, other chemokines are considered homeostatic and focus on controlling the migration of cells during normal processes of tissue development and maintenance. They are found in the vertebrates, some viruses and bacteria, but none have been found for other invertebrates.

Released from alpha-granules of activated platelets during the process of platelet aggregation, CXCL4 promotes blood coagulation by moderating the effects of heparin-like molecules. Due to the roles that it has, it has been predicted that it plays a vital role in wound repair and fixing inflammation. Usually, CXCL4 is found in a complex with proteoglycan.

Platelet factor -4 is an amino acid protein that is made up of a combination of 70 amino acids and is released from the alpha-granules of activated platelets and can bind with a high affinity to heparin. The main role that CXCL4 seems to have is to neutralize heparin-like molecules that are on the endothelial surface of blood vessels, that then inhibit local antithrombin 3 activity and promote the process of coagulation. It has been suggested that as a strong chemoattractant for neutrophils and fibroblasts, CXCL4 most probably has a role within inflammation and wound repair.

CXCL4 is chemotactic for neutrophilis, fibroblasts and monocytes, and interacts with a splice variant of the chemokine receptor CXCR3, which is known as CXCR3B.

The heparin CLCX4 complex is known as the antigen in heparin-induced thrombocytopenia, which is an idiosyncratic autoimmune reaction to the administration of the anticoagulant heparin. Auto antibodies for CLCX4 have been in found in various patients with thrombosis and features that resemble HIT but have had no previous administration of heparin.

CXCL4 is able to kill four malaria parasites within erythrocytes by selectively lysing the parasite’s digestive vacuole. Studies have shown that CXCL4 may be linked to treating malaria within the body. Recent studies have shown that having elevated levels of CXCL10 expression in the cerebrospinal fluid and peripheral blood plasma independency predicted severe and potentially fatal CM.