Activation of prorenin by proteases from polymorphonuclear leukocytes.
Inactive renin (prorenin) can be activated by certain proteases in human blood, of which a possible source in vivo is polymorphonuclear leukocytes (PMNs). We extracted enzyme from PMNs using methods established for the recovery of neutral and acid protease fractions, and tested their effectiveness on plasma prorenin in vitro. Neutral protease preparations, possessing mainly chymotrypsin and elastase activity, produce no activation of prorenin. Exogenous pancreatic alpha-chymotrypsin does activate plasma prorenin, but less effectively than trypsin. From the quantity of PMNs extracted for neutral protease, and its failure to activate protenin, we deduce that this enzyme preparation, like exogenous chymotrypsin, is qualitatively unimportant. In contrast, the extracted PMN acid protease fraction, believed to be rich in cathepsin D, exhibited high prorenin activating ability, suggesting both quantitative and qualitative importance. The low pH requirement of this acid protease (near pH 4.0), together with its inactivity at neutral pH, argues against an important systemic role in the conversion of prorenin. However, it may contribute to systemic activation in partnership with other enzymes, or else play a specialized local role in situations where PMN concentration and activity increase, and the pH is on the acid side.
D002918:Chymotrypsin / Q000097:blood; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000097:blood*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D009504:Neutrophils / Q000201:enzymology*; D010447:Peptide Hydrolases / Q000097:blood*; D012083:Renin / Q000097:blood*
D004792:Enzyme Precursors; D010447:Peptide Hydrolases; D002918:Chymotrypsin; D012083:Renin