PORCINE ORIGIN OF HUMAN SPUTUM TRYPSIN

From purulent cystic fibrosis (CF) sputum, previous investigators part ially purified a trypsinlike protease. A similar purified enzyme is av ailable commercially as ''human sputum trypsin.'' To explore the natur e and origin of this preparation, we purified and NH2 terminally seque nced its major protein component. The resulting sequence, a-Asn-Ser-Va l/Ile-Pro-Tyr-Gln-Val-Ser-Leu-Asn-Ser, differs from known human protei ns but is identical to porcine trypsin, including the Val/Ile polymorp hism at residue 12. Specific activity and electrophoretic and inhibiti on profiles and immunoreactivity of sputum and porcine pancreatic tryp sin are nearly identical. Because porcine trypsin is a major ingredien t of digestive enzyme supplements taken by CF patients with pancreatic dysfunction, we propose that one or more lots of human sputum trypsin derive from enzyme supplements and are of porcine origin. The path by which trypsin ends up in sputum is unknown. Because sputum trypsin is active but susceptible to inactivation by plasma al-proteinase inhibi tor, it is unlikely to derive from trypsin absorbed into the bloodstre am. However, it may originate from tracheally aspirated stomach conten ts or from digestive supplement-contaminated saliva mixed with expecto rated sputum. The imbalance between proteases and antiproteases in CF bronchial secretions allows trypsin to remain active despite sensitivi ty to serpins and secretory leukocyte proteinase inhibitor. Furthermor e, because sputum trypsin activates human progelatinase B, it may be r esponsible in part for the reported presence of activated matrix metal loproteinases in CF sputum.