Heparin Binding Protein

HBP

Heparin Binding Protein or HBP, also known as Cationic Antimicrobial Protein of 37kDa (CAP37) and azurocidin, is a 37kDa glycoprotein synthesised in neutrophils (1).

Structurally Heparin Binding Protein belongs to the serine protease superfamily and although it has 45% sequence identity with human neutrophil elastase, it is inactive as a protease.

HBP has a number of roles in the pathophysiology of bacterial infection including antimicrobial activity and pro-inflammatory effects on white blood cells as well as a key involvement in dysregulation of vascular function:

 

Anti-bacterial effects

HBP acts as an opsonin during infection by Gram-positive and Gram-negative bacteria and C.albicans by binding to the pathogens to enhance phagocytosis (2).

It has also been shown to bind to LPS and it is therefore possible that HBP may neutralise LPS during infection (3).

 

Inflammatory response

At the site of infection, HBP is secreted from azurophil granules during phagocytosis, where it is responsible for the recruitment and activation of monocytes and other inflammatory mediators. It is also internalised by monocytes to prolong survival and enhance cytokine production (4).

 

Vascular leakage

HBP is released from the secretory vesicles of activated neutrophils on contact with the endothelium. Once released, it induces a calcium-dependent rearrangement of the endothelial cell cytoskeleton (5), resulting in cell contraction which in turn increases permeability of the endothelium, a vital stage in the bacterial response to allow circulating white blood cells to reach the site of infection (6).

 

HBP thus directly contributes to the maintenance and progression of inflammation (7) and has therefore been proposed as a potential diagnostic and prognostic marker for the assessment of sepsis risk in infected patients (8).

For further details on the use of HBP in sepsis assessment and a summary of several key trials please see the Clinical Utility page.

 

References

1. Tapper H et al Blood 2002; 99: 1785-1793

2. Soehnlein O J Mol Med 2009; 87(12): 1157-84

3. Pereira H et al J Clin Invest 1990; 85: 1468-1476

4. Heinzelmann M et al J Immunol 1998; 160: 5530-36

5. Gautam N et al Nature Medicine 2001; 7(10): 1123-1127

6. Muller WA Vet Pathol 2013; 50(1): 7-22

7. Linder A, Soehnlein O, Akesson P J Innate Immun 2010; 2(5): 431-8

8. Linder A et al Crit Care Med 2015; 43(11)