Codistribution of TAP and the granule membrane protein GRAMP-92 in rat caerulein-induced pancreatitis.
The pathological activation of zymogens within the pancreatic acinar cell plays a role in acute pancreatitis. To identify the processing site where activation occurs, antibodies to the trypsinogen activation peptide (TAP) were used in immunofluorescence studies using frozen sections from rat pancreas. Saline controls or animals receiving caerulein in amounts producing physiological levels of pancreatic stimulation demonstrated little or no TAP immunoreactivity. However, after caerulein hyperstimulation (5 micrograms. kg-1. h-1) for 30 min and the induction of pancreatitis, TAP immunoreactivity appeared in a vesicular, supranuclear compartment that demonstrated no overlap with zymogen granules. The number of vesicles and their size increased with time. After 60 min of hyperstimulation with caerulein, most of the TAP reactivity was localized within vacuoles >/=1 micrometer that demonstrated immunoreactivity for the granule membrane protein GRAMP-92, a marker for lysosomes and recycling endosomes. Pretreatment with the protease inhibitor FUT-175 blocked the appearance of TAP after hyperstimulation. These studies provide evidence that caerulein hyperstimulation stimulates trypsinogen processing to trypsin in distinct acinar cell compartments in a time-dependent manner.
Otani
T
T
Department of Medicine and Cell Biology, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut 06516, USA.
Chepilko
S M
SM
Grendell
J H
JH
Gorelick
F S
FS
D000208:Acute Disease; D000818:Animals; D015415:Biomarkers; D002108:Ceruletide / Q000633:toxicity*; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism*; D015388:Organelles / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014362:Trypsinogen / Q000378:metabolism; D014617:Vacuoles / Q000187:drug effects / Q000378:metabolism
D015415:Biomarkers; D008565:Membrane Proteins; D009842:Oligopeptides; C080396:trypsinogen activation peptide; D002108:Ceruletide; D014362:Trypsinogen