Natural resistance of W/Wv mice to ethanol-induced gastric lesions and its abrogation by bone marrow grafting: possible role of mast cells and LTC4.
The extent of ethanol-induced acute gastric lesions, gastric leukotriene C4 (LTC4) levels, and the number of gastric mucosal mast cells were examined in mast cell-deficient W/Wv mice, normal litter-mate +/+ mice, and bone marrow-reconstituted W/Wv mice. After administration of ethanol, +/+ mice developed gastric lesions and elevation of gastric LTC4 levels in a dose dependent manner. In mast cell-deficient W/Wv mice, the extent of gastric lesions was far less than that of +/+ mice and the level of gastric LTC4 was not significantly altered. This difference was not due to anemia because blood-transfused non-anemic W/Wv mice were still resistant to ethanol-induced gastric lesions. When W/Wv mice were reconstituted with +/+ bone marrow cells, their natural resistance against ethanol-induced gastric lesions was abrogated. The extent of gastric lesions of bone marrow-reconstituted W/Wv mice paralleled with the increase in number of gastric mucosal mast cells and also with the level of gastric LTC4. Furthermore, ethanol-induced gastric lesions in bone marrow-reconstituted W/Wv mice was inhibited by pretreatment with 5-lipoxygenase inhibitor, AA-861, in a dose dependent manner. These results suggest that LTC4 may, even if it is not a prerequisite factor for ethanol induced acute gastric lesions, act as the amplitier in the sequential events of the pathogenesis.
Higa
A
A
First Department of Internal Medicine, Miyazaki Medical College, Japan.
Yoshida
T
T
Tanaka
K
K
Abe
T
T
Nawa
Y
Y
D000818:Animals; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002452:Cell Count; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D000431:Ethanol / Q000008:administration & dosage / Q000009:adverse effects*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D013189:SRS-A / Q000502:physiology*; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000517:prevention & control
D013189:SRS-A; D000431:Ethanol