Does resistance to endotoxin in primates correlate with levels of plasma prekallikrein?

Increased release of BK by HK hydrolysis has been correlated with the severity of hypotension in septic patients and animals challenged with gram-negative bacteria or endotoxin (ETX). Since HK hydrolysis in vivo is attributed mainly to the catalytic reaction of kallikrein (KAL) formed by activation of plasma PK, I tested whether the known resistance to ETX-rhesus and baboon > man and chimp-correlated with PK levels. Immunoblots and amidolytic assays showed that PK levels did not correlate. They were in rhesus and man > baboon and chimp. Also, PK did not correlate with levels of other modulators of free KAL levels in plasma-factor XII, HK and KAL inhibitors. Nonetheless, the distribution of PK and its activation products in plasmas activated with kaolin at 37 degrees C is analogous in the 4 primates, suggesting a similar mechanism for KAL inhibition in vitro. The results suggest that factors not yet known must contribute to the differential resistance of primates to ETX. Knowledge of these factors will help in prophylaxis and therapy of septicemia.