Activation of prorenin by proteases from polymorphonuclear leukocytes

Area of Science:

• Biochemistry
• Physiology
• Enzymology

Background:

• Inactive renin (prorenin) circulates in human blood.
• Polymorphonuclear leukocytes (PMNs) are a potential source of proteases that activate prorenin in vivo.
• Understanding prorenin activation is crucial for studying the renin-angiotensin system.

Purpose of the Study:

• To investigate the prorenin-activating capacity of enzymes extracted from PMNs.
• To determine the relative importance of neutral and acid protease fractions from PMNs in prorenin activation.

Main Methods:

• Enzymes were extracted from PMNs into neutral and acid protease fractions.
• The ability of these fractions to activate plasma prorenin in vitro was tested.
• Exogenous pancreatic alpha-chymotrypsin and trypsin were used as controls.

Main Results:

• Neutral protease fractions from PMNs showed no prorenin activation.
• Exogenous alpha-chymotrypsin activated prorenin, but less effectively than trypsin.
• The PMN acid protease fraction, rich in cathepsin D, demonstrated significant prorenin activating ability.
• This acid protease functions optimally at a low pH (around 4.0) and is inactive at neutral pH.

Conclusions:

• The acid protease from PMNs is quantitatively and qualitatively important for prorenin activation.
• Its low pH optimum suggests a specialized local role rather than a major systemic function.
• PMN acid protease may contribute to systemic prorenin activation in conjunction with other enzymes or in specific localized conditions.