Endopeptidase inhibition and intestinal antigen processing in mice.
The role of gastrointestinal digestive processes in the systemic availability of ingested protein antigens was examined by feeding the trypsin inhibitor aprotinin intragastrically to mice and measuring uptake of ovalbumin and 14C-polyethylene glycol (MW 4000) from the gastrointestinal tract. Trypsin and chymotrypsin activities in the intestinal lumen were significantly reduced by aprotinin feeding. Aprotinin slowed stomach emptying, but radioimmunoassays for immunoreactive ovalbumin in the serum of mice prefed aprotinin showed 12-fold elevations within 1 hr after ovalbumin feeding. Uptake of a nonmetabolized macromolecular probe, 14C-polyethylene glycol-4000, increased less than two-fold when fed with aprotinin under the same conditions, indicating that the increased uptake of immunoreactive ovalbumin was not due to changes in intestinal permeability. The results show that inhibition of luminal proteolysis caused significant increases in the serum concentration of immunoreactive ovalbumin, indicating that acute inhibition of luminal proteases permits larger quantities of relatively intact protein to interact with mucosal absorptive surfaces. These results support the hypothesis that pancreatic proteases modulate antigen absorption from the lumen in adult animals.
Hanson
D G
DG
Department of Pediatrics, Harvard Medical School, Boston, MA.
Roy
M J
MJ
Miller
S D
SD
Seidman
E G
EG
Thomas
M J
MJ
Sanderson
I R
IR
Udall
J N
JN
Ely
I
I
Green
G M
GM
D000818:Animals; D017951:Antigen Presentation; D007611:Aprotinin / Q000494:pharmacology*; D002463:Cell Membrane Permeability; D002918:Chymotrypsin / Q000378:metabolism; D004064:Digestive System / Q000378:metabolism; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects; D007408:Intestinal Absorption / Q000276:immunology*; D007421:Intestine, Small / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D011092:Polyethylene Glycols / Q000378:metabolism; D011863:Radioimmunoassay; D014357:Trypsin / Q000378:metabolism
D011092:Polyethylene Glycols; D010047:Ovalbumin; D007611:Aprotinin; D002918:Chymotrypsin; D014357:Trypsin