Role of the high affinity immunoglobulin E receptor in bacterial translocation and intestinal inflammation - PubMed (original) (raw)

Role of the high affinity immunoglobulin E receptor in bacterial translocation and intestinal inflammation

D Dombrowicz et al. J Exp Med. 2001.

Abstract

A role for immunoglobulin E and its high affinity receptor (Fc epsilon RI) in the control of bacterial pathogenicity and intestinal inflammation has been suggested, but relevant animal models are lacking. Here we compare transgenic mice expressing a humanized Fc epsilon RI (hFc epsilon RI), with a cell distribution similar to that in humans, to Fc epsilon RI-deficient animals. In hFc epsilon RI transgenic mice, levels of colonic interleukin 4 were higher, the composition of fecal flora was greatly modified, and bacterial translocation towards mesenteric lymph nodes was increased. In hFc epsilon RI transgenic mice, 2,4,6-tri-nitrobenzenesulfonic acid (TNBS)-induced colitis was also more pronounced, whereas Fc epsilon RI-deficient animals were protected from colitis, demonstrating that Fc epsilon RI can affect the onset of intestinal inflammation.

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Figures

Figure 1

Figure 1

Expression of FcεRIα transcripts (top), β-actin (middle), and IgE productive transcripts (pε; bottom) in hFcεRIα Tg, WT, and FcεRIα−/− mice. Ethidium bromide–stained agarose gels were loaded with amplified PCR products from individual mice.

Figure 2

Figure 2

Histology of colon mucosa from hFcεRIα Tg, WT, and FcεRIα−/− mice after May-Grünwald/Giemsa staining of paraffin-embedded 4-μm sections. Bars, 0.2 mm.

Figure 3

Figure 3

Cytokine mRNA levels in the colon of hFcεRIα Tg, WT, and FcεRIα−/− mice. IFN-γ, IL1-β, TNF-α, IL-10, and IL-4 were quantified by competitive RT-PCR from colon mRNA (n = 13 for FcεRIα Tg mice, n = 13 for WT mice, and n = 6 for FcεRIα−/− mice). Results are expressed as number of cytokine mRNA molecules per 104 molecules of β-actin. Individual values, mean, and SD are represented.

Figure 4

Figure 4

Intestinal permeability in hFcεRIα Tg, WT, and FcεRIα−/− mice. Lactulose/mannitol and lactulose/sucralose ratio in the urine collected over a 24-h period after gavage. Bars represent pools from five mice.

Figure 5

Figure 5

Luminal (a) and MLN (b) flora from hFcεRIα Tg, WT, and FcεRIα−/− mice. Germ number in feces from the three strains of mice were analyzed after culture of both aerobic and anaerobic flora. Results are expressed as mean numbers of bacteria per gram of feces or tissue ± SD (n = 7 for hFcεRIα Tg, n = 8 for WT, and n = 15 for FcεRIα−/− mice; *P < 0.05). Error bars (a) are falling within the top line of each histogram.

Figure 6

Figure 6

Macroscopic (a) and microscopic (b) evaluations of colons from hFcεRIαTg, WT, and FcεRIα−/− mice 48 h after intrarectal TNBS administration. Colons were open along the longitudinal axis for photography. (a) Colons of TNBS-treated hFcεRIα Tg mice display intense inflammation with edema and necrosis compared with the mild inflammation observed in the colon of WT animals and to the absence of inflammation in colons from TNBS-treated FcεRIα−/− mice. One representative colon for each strain of mice is shown. Distal colon is on the left side. (b) 4-μm paraffin-embedded sections were stained with May-Grünwald/Giemsa. Bar, 0.2 mm.

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