Roles of Heparin-Binding Protein in Bacterial Infections

Abstract

Infectious diseases remain a major health problem, where sepsis and other severe infectious diseases are common causes of morbidity and mortality. The importance of early and appropriate treatment of sepsis and severe bacterial infections has been underlined by the successes of measures like the Surviving Sepsis Campaign, among others. Thus, there is a need for clinical and laboratory tools to identify a patient with severe infection early and to distinguish between bacterial and non-bacterial conditions. Heparin-binding protein (HBP) is also called azurocidin, or cationic antimicrobial protein of 37 kDa (CAP37). It is a multifunctional granule-associated protein that is rapidly mobilized from migrating polymorphonuclear leukocytes. HBP acts as a chemoattractant, an activator of monocytes and macrophages, and induces vascular leakage and edema formation. The release of HBP is triggered by ligation of neutrophilic β₂-integrins, a process that may be initiated by bacterial structures. The overall outcome is powerful vascular leakage. It has been shown that patients with severe sepsis express high levels of HBP in plasma before they develop hypotension. HBP is also involved in the pathophysiology of soft tissue infection. In conclusion, this protein is strongly involved in the pathophysiology of severe bacterial infections, and thus represents a potential diagnostic marker and a target for treatment.

Diagnostic accuracy of urine heparin binding protein for pediatric acute pyelonephritis

“…HBP is a cytokine released from activated neutrophils by bacterial stimulation of β 2 -integrins ligation [10]. Our results are consistent with the previous findings by Kjolvmark et al that UHBP levels of >32 ng/mL are the optimal cutoff for UTI Fig.…”

“…Various bacterial infections, including APN and urosepsis, stimulate the release of HBP into the systemic circulation [10,3]. A recent study showed that urine HBP (UHBP) provided better sensitivity and specificity compared to urine dipstick analysis in children with upper or lower urinary tract infection (UTI) [8].…”

Contribution of Neutrophils to Acute Lung Injury

“…However, antibodies which are found in TRALI have been shown to trigger discharge of azurocidin from neutrophils (192). In addition, in circumstances that may lead to ALI such as severe burns or sepsis, circulating azurocidin levels are increased significantly, allowing speculation on their potential role in lung damage (193)(194)(195).…”

Binding host proteins to the M protein contributes to the mortality associated with influenza–Streptococcus pyogenes superinfections

“…In addition, patients with severe infection typically suffer from acute lung injury resulting in increased pulmonary microvascular leakage [10]. This is also associated with an increase in plasma levels of heparinbinding protein (HBP; also called azurocidin or CAP37), a granule-associated protein secreted by polymorphonuclear leukocytes (PMNs), and an increase in the risk of bacteraemia [11][12][13][14]. Furthermore, IAV infection elicits a thrombotic inflammatory response, which increases the abundance of fibrinogen (Fg)/fibrin and fibronectin (Fn) in the lung [15].…”