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Azurocidin (Cationic Antimicrobial Protein 37 kDa, CAP37, Heparin-Binding Protein, HBP)

Azurocidin, also known as cationic antimicrobial protein 37 kDa (CAP37) or heparin-binding protein (HBP) is an inactive homolog of serine proteinases residing in granulocytes. The ability to cleave peptide bond was lost due to replacement of two of the three residues from the conserved catalytic triad characteristic for serine proteinases. Azurocidin is a single polypeptide glycoprotein synthesized as a 251 amino-acid precursor which is subsequently processed by removal of 26 amino-acid residues from the N-terminus and three residues from the C-terminus. The mature polypeptide consists of 222 amino-acid residues with calculated molecular mass of 24 kDa. Azurocidin is an example of a protein which lost its primary proteolytic function in evolution, but gained another activity — it became an important mediator of inflammatory response. As a component of neutrophil azurophilic granules it participates in oxygen-independent killing mechanisms functioning in phagocytosing neutrophils. Azurocidin has a broad spectrum of antimicrobial activity, mainly against Gram-negative bacteria. Released extracellularly, azurocidin causes contraction of endothelial cells. Secreted azurocidin attracts monocytes and is responsible for their influx into inflammation sites. These properties make azurocidin a plausible target in new therapies directed against the harmful effects of inflammatory response. Azurocidin is promising biomarker for identification of patients who are at risk in developing sepsis. Plasma HBP levels correlate with the severity of infection and, in particular, with the development of circulatory failure. There is close correlation between increased HBP plasma levels and the development of hypotension, organ failure, and septic shock. Due to its antimicrobial features, elevated cerebrospinal fluid levels of HBP distinguish between patients with acute bacterial meningitis and patients with other central nervous system infections.

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