About CXCL7 / NAP2:
Chemokine (C-X-C motif), also know as ligand 7 and CXCL7 is a human gene that has an encoded protein which is a small cytokine which belongs to the CXC chemokine family.
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.
A group of small cytokines - signalling proteins that come from the cells - chemokines have the ability to induce direct chemotaxis within nearby cells that are responsive cells. These responsive cells are known as 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 usually 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.
This particular encoded protein, CXCL7 is an isoform of Beta-Thromboglobulin, which is also known as Pro-Platelet basic protein or PPBP. CXCL7 is a protein that tends to be released in large numbers from the platelets following their activation. What this gene does is stimulate a range of processes, which includes mitogenesis, synthesis of extracellular matrix, glucose metabolism, and synthesis of plasminogen activator.
Usually created during platelet development and stored within the platelet granules and quickly released during platlet degranulation, CXCL4 and CXCL7 are the first chemokines to appear at areas of tissue damage, injury and infection, this is particularly true when there is a hemorrhage and/or vascular damage, and are able to reach very high concentrations.
CXCL7 is activated by the sequential proteolysis within its N terminus. The prepropeptide form of this , known as platelet basic protein (92 aa) is cut down during platelet maturation so that it can produce the platelet maturation that produces 85 aa major stored form, named connective tissue activating peptide-3, which is inactive on neutrophils. During degranulation, this is further processed into 81 aa B-thromboglobulin, which is also inactive. This can then be cleaved by a special cell surface-bound cathepsin G-like enzyme on neutrophils, to create 70 aa CXCL7, which has higher homology compared to CXCL4 by 70%.
Thus, CXCL7 is able to work as an immediate-early mediator of neutrophil recruitment which is released from the platelets at sites of inflammation. Although it isn’t a prominent leukocyte chemoattractant and doesn’t induce degranulation of neutrophil lysosomal enzymes, CXCL4 can induce secondary granule exocytosis and also release matrix-degrading enzymes that allow neutrophil penetration of any infection or damaged tissues within the body.