HEPARIN INTERFERES WITH THE INHIBITION OF NEUTROPHIL ELASTASE BY ITS PHYSIOLOGICAL INHIBITORS

Heparin depresses the second-order rate constant k(ass) for the inhibition of neutrophil elastase by alpha-1-proteinase inhibitor. For high and low molecular weight heparin the decrease in k(ass) is 290-fold and 40-fold, respectively. This is due to a tight binding of the polymer to elastase : K(d) = 3.3 nM or 89 nM for high or low molecular weight heparin respectively. In contrast heparin increases the rate of inhibition of elastase by mucus proteinase inhibitor. For low molecular weight heparin, there is a 27-fold increase in k(ass), This is due to a strong binding of the polymer to the inhibitor (K(d) = 50 nM) which undergoes a conformational change.