Alpha(1)-antitrypsin and antichymotrypsin in human milk: origin, concentrations, and stability.
BACKGROUND
The protease inhibitors alpha(1)-antitrypsin and antichymotrypsin are present in human milk, but little is known about their roles in protein digestion during infancy. It has been hypothesized that alpha(1)-antitrypsin and antichymotrypsin may modulate digestion in the infant gut.


OBJECTIVE
We determined whether the mammary gland expresses alpha(1)-antitrypsin and antichymotrypsin, measured alpha(1)-antitrypsin and antichymotrypsin throughout lactation, assessed the resistance of alpha(1)-antitrypsin to proteolysis, and determined the potential of alpha(1)-antitrypsin to affect the survival of other milk proteins.


METHODS
A pool of complementary DNA from the human mammary gland was analyzed with polymerase chain reaction to detect genes for alpha(1)-antitrypsin and antichymotrypsin. alpha(1)-Antitrypsin and antichymotrypsin concentrations were measured in milk samples obtained longitudinally (days 4-47) from 8 women. An in vitro model of infant digestion was used to assess the digestive stability of alpha(1)-antitrypsin against pepsin and pancreatin. Lactoferrin, with alpha(1)-antitrypsin present, was digested by pancreatin, and the digested proteins were separated.


RESULTS
Alpha(1)-antitrypsin and antichymotrypsin concentrations were high in early milk and decreased throughout lactation. Polymerase chain reaction products were detected for both genes. After in vitro digestion, much of the alpha(1)-antitrypsin was still intact, whereas many other milk proteins were digested. Much of the lactoferrin was still intact after digestion, but only when alpha(1)-antitrypsin was added.


CONCLUSIONS
The results suggest that alpha(1)-antitrypsin and antichymotrypsin are produced by the mammary gland and are present in milk in relatively high amounts in early lactation. alpha(1)-Antitrypsin may survive digestion and may affect the survival of other proteins.
D001940:Breast / Q000378:metabolism; D002918:Chymotrypsin / Q000037:antagonists & inhibitors*; D018076:DNA, Complementary / Q000032:analysis; D004355:Drug Stability; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000032:analysis / Q000378:metabolism; D005260:Female; D006801:Humans; D007781:Lactoferrin / Q000378:metabolism; D008137:Longitudinal Studies; D008894:Milk Proteins / Q000032:analysis / Q000378:metabolism; D008895:Milk, Human / Q000737:chemistry*; D010194:Pancreatin / Q000378:metabolism; D010434:Pepsin A / Q000378:metabolism; D016133:Polymerase Chain Reaction; D013997:Time Factors; D000067816:Whey Proteins; D000515:alpha 1-Antitrypsin / Q000032:analysis* / Q000235:genetics / Q000378:metabolism
D018076:DNA, Complementary; D004791:Enzyme Inhibitors; D008894:Milk Proteins; D000067816:Whey Proteins; D000515:alpha 1-Antitrypsin; D010194:Pancreatin; D007781:Lactoferrin; D002918:Chymotrypsin; D010434:Pepsin A