Eosinophilic gastroenterocolitis with peripheral eosinophilia was induced in rats fed a diet containing 2.5% or 5.0% iron lactate for 3 mo. Additional findings consistent with iron overload were also observed. Microscopically, the lesions consisted of eosinophilic infiltrations in the mucosa and submucosa along the whole length of the gastrointestinal tracts, increased surface area of the gastric mucosal propria covered with mucous cells, and increased apoptotic bodies in the gastric glandular neck of rats in the 2.5% and 5.0% groups. An increased number of intraepithelial globule leukocytes in the gastric and intestinal lamina propria was also observed in the 5.0% group. Globule leukocytes in the gastric mucosa contained obviously enlarged granules in their cytoplasm in these rats. The granules of the globule leukocytes were positive for rat mast cell protease II, suggesting the mastocyte origin of these cells. Although severe infiltration of eosinophils and globule leukocytes suggested a type-1 hypersensitivity reaction, other features such as an increasing vascular permeability were not detected. Serum IgE levels in the 5.0% and control groups were <3 ng/ml. Final body weights of male and female rats of the 5.0% group were suppressed to 70% and 90%, respectively, of those of the control rats, whereas food consumption was comparable to that of the control group. The morphologic characteristics of the gastrointestinal lesions and peripheral eosinophilia induced in rats fed iron lactate were very similar to those in some cases of eosinophilic gastroenterocolitis in humans and other animals.
Arizono N., Kasugai T., Yamada M., Okada M., Morimoto M., Tei H., Newlands GF, Miller HR, and Kitamura Y. (1993). Infection of Nippostrongylus brasiliensis induces development of mucosal-type but not connective tissue-type mast cells in genetically mast cell-deficient Ws/Ws rats. Blood81: 2572-2578.
2.
Baert J. (1987). Isolation and cytochemical characterization of globule leukocytes from rat tracheal epithelium. Anat. Rec.219: 78-85.
3.
Baert J. and Frederix M. (1985). Globule leukocytes in the respiratory epithelium of human upper airways: An ultrastructural study. Anat. Rec.212: 143-152.
4.
Bauer S., Schaub N., Kummer H., and Wegmann W. (1994). Prolonged course of an idiopathic hypereosinophilic syndrome with transition to eosinophilic gastroenteritis. Schweiz. Med. Wochenschr.124: 1976-1981.
5.
Bischoff SC (1996). Mucosal allergy: Role of mast cells and eosinophil granulocytes in the gut. Baillieres Clin. Gastroenterol.10: 443-459.
6.
Boismenu R. and Havran L. (1994). Modulation of epithelial cell growth by intaepithelial γδ cells. Science266: 1253-1255.
7.
Breider MA, Kiely RG, and Edwards JF (1985). Chronic eosinophilic pancreatitis and ulcerative colitis in a horse. J. Am. Vet. Med. Assoc.186: 809-811.
8.
Caldwell JH, Mekhjian HS, Hurtubise PE, and Beman FM (1978). Eosinophilic gastroenteritis with obstruction. Immunological studies of seven patients. Gastroenterology74: 825-828.
9.
Dabbagh AJ, Mannion T., Lynch SM, and Frei B. (1994). The effect of iron overload on rat plasma and liver oxidant status in vivo. Biochem. J.300: 799-803.
10.
DeSchryver-Kecskemeti K. and Clouse RE (1984). A previously unrecognized subgroup of "eosinophilic gastroenteritis." Association with connective tissue diseases. Am. J. Surg. Pathol.8: 171-180.
11.
Douch PG (1989). The effects of immunization of sheep with Trichostrongylus colubriformis larvae on worm burdens acquired during grazing. Int. J. Parasitol.19: 177-181.
12.
Fields M., Lewis CG, Lure MD, and Burns WA (1995). Dietary ferric vs. ferrous iron in copper-deficient rats fed fructose-based diets. J. Am. Coll. Nutr.14: 399-403.
13.
Fields M., Lewis CG, Lure MD, Bums WA, and Antholine WE (1993). Low dietary iron prevents free radical formation and heart pathology of copper-deficient rats fed fructose. Proc. Soc. Exp. Biol. Med.202: 225-232.
14.
Griffin HE and Meunier LD (1990). Eosinophilic enteritis in a specific-pathogen-free cat. J. Am. Vet. Med. Assoc.197: 619-620.
15.
Halliday JW and Searle J. (1996). Hepatic iron deposition in human disease and animal models. Biometals9: 205-209.
16.
Hayden DW and Van Kruiningen HJ (1973). Eosinophilic gastroenteritis in German Shepherd Dogs and its relationship to visceral larva migrans. J. Am. Vet. Med. Assoc.162: 379-384.
17.
Hayden DW and Van Kruiningen HJ (1975). Experimentally induced canine toxocariasis: Laboratory examinations and pathologic changes, with emphasis on the gastrointestinal tract. Am. J. Vet. Res.36: 1605-1614.
Henderic M. (1981). A spectrum of hypereosinophilic syndromes exemplified by six cats with eosinophilic enteritis. Vet. Pathol.18: 188-200.
20.
Home WI, Tandler B., Dubick MA, Niemela O., Brittenham GM, and Tsukamoto H. (1997). Iron overload in the rat pancreas following portacaval shunting and dietary iron supplementation. Exp. Mol. Pathol.64: 90-102.
21.
Iancu TC, Ward RJ, and Peters TJ (1987). Ultrastructural observations in the carbonyl iron-fed rat, an animal model for hemochromatosis. Virchows Arch. B Cell Pathol. Incl. Mol. Pathol.53: 208-217.
22.
Ikeda Y. and Yamashina S. (1993). Developmental changes in intestinal globule leukocytes of normal rats. Cell. Tissue Res.273: 447-455.
23.
Karademir S. , Akcayoz A., Bek K., Tanyel FC, Sungur M., Celik I., and Ural C. (1995). Eosinophilic gastroenteritis presenting as protein-losing enteropathy (case report). Turk. J. Pediatr.37: 45-50.
24.
Kim IY, Mitchell DG, Vinitski S., Consigny PM, Hann HW, Rifkin MD, and Rubin R. (1993). MR imaging of hepatic iron overload in rat. J. Magn. Reson. Imaging3: 67-70.
25.
Komano H., Fujiura Y., Kawaguchi M., Matsumoto S., Hashimoto Y., Obana S., Mombaerts P., Tonegawa S., Yamamoto H., Itohara S., Nan-no M., and Ishikawa H. (1995). Homeostatic regulation of intestinal epithelia by intraepithelial γδ T cells. Proc. Natl. Acad. Sci. USA92: 6147-6151.
26.
Konno A., Hashimoto Y., Kon Y., Okada K., Davis WC, and Sugimura M. (1995). Expression of γδ T cell receptor on caprine globule leukocytes. Vet. Immunol. Immunopathol.48: 105-112.
27.
Lee M., Hodges WG, Huggins TL, and Lee EL (1996). Eosinophilic gastroenteritis. South. Med. J.89: 189-194.
28.
Luna LC ( 1968). Luna's method for erythrocytes and eosinophil granules . In: Histologic Staining Methods of theArmed Forces Institute of Pathology, 3rd. ed. McGraw-Hill, New York, pp. 111-112.
29.
Matsushita M., Hajiro K., Morita Y., Takakuwa H., and Suzaki T. (1995). Eosinophilic gastroenteritis involving the entire digestive tract. Am. J. Gastroenterol.90: 1868-1870.
30.
McNabb PC, Fleming CR, Higgins JA, and Davis GL (1979). Transmural eosinophilic gastroenteritis with ascites . Mayo Clin. Proc.54: 119-122.
31.
Meshkinpour H., Vaziri ND, Zhou XJ, Erickson R., Liao SY, Oveisi F., Bemanian S., and Hollander D. (1996). Effects of experimental hemosiderosis on intestinal morphology, permeability, and tissue iron content . Dig. Dis. Sci.41: 984-988.
32.
Narama I., Kuroda J., Nagatani M., Miura K., Katoh T., and Tsuchitani M. (1990). Superficial eosinophilic gastritis in laboratory Beagle dogs attributable probably to diet. Jpn. J. Vet. Sci.52: 581-589.
33.
Park CH, Bacon BR, Brittenham GM, and Tavill AS (1987). Pathology of dietary carbonyl iron overload in rats. Lab. Invest.57: 555-563.
34.
Pass DA and Bolton JR (1982). Chronic eosinophilic gastroenteritis in the horse . Vet. Pathol.19: 486-496.
35.
Quigley PJ and Henry K. (1981). Eosinophilic enteritis in the dog: A case report with a brief review of the literature. J. Comp. Pathol.91: 387-392.
36.
Reynolds CW , Timonen T., and Herberman RB (1981). Natural killer (NK) cell activity in the rat. 1. Isolation and characterization of the effector cells . J. Immunol.127: 282-287.
37.
Stal P., Hultcrantz R., Moller L., and Eriksson LC (1995). The effects of dietary iron on initiation and promotion in chemical hepatocarcinogenesis. Hepatology21: 521-528.
38.
Stal P., Johansson I., Ingelman-Sundberg M., Hagen K., and Hultcrantz R. (1996). Hepatotoxicity induced by iron overload and alcohol. Studies on the role of chelatable iron, cytochrome P450 2E1 and lipid peroxidation . J. Hepatol.25: 538-546.
39.
Talley NJ, Shorter RG, Phillips SF, and Zinsmeister AR (1990). Eosinophilic gastroenteritis: A clinicopathological study of patients with disease of the mucosa, muscle layer, and subserosal tissues. Gut31: 54-58.
40.
Tam EK, Calonico LD, Nadel JA, and McDonald DM (1988). Globule leukocytes and mast cells in the rat trachea: Their number, distribution, and response to compound 48/80 and dexamethasone . Anat. Embryol. Berl.178: 107-118.
41.
Whittaker P. , Dunkel VC, Bucci TJ, Kusewitt DF, Thurman JD, Warbritton A., and Wolff GL (1997). Genome-linked toxic responses to dietary iron overload. Toxicol. Pathol.25: 556-564.
42.
Whittaker P. , Hines FA, Robl MG, and Dunkel VC (1996). Histopathological evaluation of liver, pancreas, spleen, and heart from iron-overloaded Sprague-Dawley rats. Toxicol. Pathol.24: 558-563.
43.
Wiggin CJ and Gibbs HC (1990). Adverse immune reactions and the pathogenesis of Ostertagia ostertagi infections in calves. Am. J. Vet. Res.51: 825-832.
44.
Wing-Harkins DL, Dellinger GW, Lynch C., and Mihas AA (1996). Eosinophilic gastro-enteritis associated with protein-losing enteropathy and protein C deficiency. J. Int. Med. Res.24: 155-163.
