The bacterial flora of α-Gal knockout mice express the α-Gal epitope comparable to wild type mice

被引:7
作者
Dahl, K
Kirkeby, S
d'Apice, AFJ
Mathiassen, S
Hansen, AK
机构
[1] Royal Vet & Agr Univ, Dept Vet Pathobiol, Div Lab Anim Sci & Welf, DK-1870 Frederiksberg, Denmark
[2] Univ Copenhagen, Sch Dent, Inst Oral Med, DK-2200 Copenhagen, Denmark
[3] St Vincents Hosp, Immunol Res Ctr, Fitzroy, Vic 3065, Australia
[4] Univ Copenhagen, Dept Expt Med, DK-2200 Copenhagen, Denmark
关键词
xenotransplantation; alpha-Gal knockout mice; alpha-Gal epitope; microflora; Enterobacteriaceae spp;
D O I
10.1016/j.trim.2004.11.002
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The human genome possesses pseudogenes for the enzyme a 1,3 galactosyltransferase and hence, human cells and tissues do not express the Gala terminated trisaccharide structure Gal alpha 1-3Gal beta 1-4GlcNAc, the so-called a-Gal epitope. Circulating antibodies specific for this carbohydrate epitope are, however, present in high amounts in humans. It has previously been hypothesized that the antibody production is induced by the presence of the a-Gal epitope in the cell walls of the enteric flora, especially Enterobacteriaceae spp. However, in mice, in which the epitope has been deleted by targeted mutation of the gal-transferase gene, a-Gal antibodies do not appear without prior immunization, although the mice through their growth probably have been exposed to a normal bacterial flora of e.g. Enterobacteriaceae spp. It is unknown whether there are different types of immune reactions to antigenic carbohydrate expressing bacteria and whether there are discrepancies in the enteric flora between these knockout mice and their wild type litter mates. In this study the enteric flora of a-Gal knockout and wild type mice was compared both in relation to the prevalence of different types of bacteria in the two groups of mice, as well as in relation to the expression of the epitope on the surface of Enterobacteriaceae spp. Our results showed that the enteric flora did not differ significantly between knockout and wild type mice and that it was comparable to the flora known to be present in the intestines of other mice. All Enterobacteriaceae spp. examined expressed the a-Gal epitope no matter whether they were isolated from knockout or wild type mice. It is, therefore, discussed whether it is more reasonable to assume that a-Gal antibodies in mammals that do not produce alpha 1,3 galactosyltransferase such as in the knock mice and in humans are the result of another antigen stimulant than these common representatives of the enteric flora, that we isolated from the two types of mice. Possible candidates for a carrier in humans could be bacteria or viruses not isolated from barrier-bred mice. (c) 2004 Elsevier B.V. All rights reserved.
引用
收藏
页码:9 / 16
页数:8
相关论文
共 22 条
[1]   Targeted disruption of the α1,3-galactosyltransferase gene in cloned pigs [J].
Dai, YF ;
Vaught, TD ;
Boone, J ;
Chen, SH ;
Phelps, CJ ;
Ball, S ;
Monahan, JA ;
Jobst, PM ;
McCreath, KJ ;
Lamborn, AE ;
Cowell-Lucero, JL ;
Wells, KD ;
Colman, A ;
Polejaeva, IA ;
Ayares, DL .
NATURE BIOTECHNOLOGY, 2002, 20 (03) :251-255
[2]   Enhancement of antigen presentation of influenza virus hemagglutinin by the natural human anti-Gal antibody [J].
Galili, U ;
Repik, PM ;
Anaraki, F ;
Mozdzanowska, K ;
Washko, G ;
Gerhard, W .
VACCINE, 1996, 14 (04) :321-328
[3]   A UNIQUE NATURAL HUMAN-IGG ANTIBODY WITH ANTI-ALPHA-GALACTOSYL SPECIFICITY [J].
GALILI, U ;
RACHMILEWITZ, EA ;
PELEG, A ;
FLECHNER, I .
JOURNAL OF EXPERIMENTAL MEDICINE, 1984, 160 (05) :1519-1531
[4]   INTERACTION BETWEEN HUMAN NATURAL ANTI-ALPHA-GALACTOSYL IMMUNOGLOBULIN-G AND BACTERIA OF THE HUMAN FLORA [J].
GALILI, U ;
MANDRELL, RE ;
HAMADEH, RM ;
SHOHET, SB ;
GRIFFISS, JM .
INFECTION AND IMMUNITY, 1988, 56 (07) :1730-1737
[5]  
GALILI U, 1993, SPRINGER SEMIN IMMUN, V15, P155
[6]   HUMAN NATURAL ANTI-GAL IGG REGULATES ALTERNATIVE COMPLEMENT PATHWAY ACTIVATION ON BACTERIAL SURFACES [J].
HAMADEH, RM ;
JARVIS, GA ;
GALILI, U ;
MANDRELL, RE ;
ZHOU, P ;
GRIFFISS, JM .
JOURNAL OF CLINICAL INVESTIGATION, 1992, 89 (04) :1223-1235
[7]   ANTI-ALPHA-GALACTOSYL IMMUNOGLOBULIN-A (IGA), IGG, AND IGM IN HUMAN SECRETIONS [J].
HAMADEH, RM ;
GALILI, U ;
ZHOU, P ;
GRIFFISS, JM .
CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY, 1995, 2 (02) :125-131
[8]   ANTI-GAL BINDS TO PILI OF NEISSERIA-MENINGITIDIS - THE IMMUNOGLOBULIN-A ISOTYPE BLOCKS COMPLEMENT-MEDIATED KILLING [J].
HAMADEH, RM ;
ESTABROOK, MM ;
ZHOU, P ;
JARVIS, GA ;
GRIFFISS, JM .
INFECTION AND IMMUNITY, 1995, 63 (12) :4900-4906
[9]  
HANSEN AK, 1999, HDB LAB ANIMAL BACTE
[10]   Lectin interactions with α-galactosylated xenoantigens [J].
Kirkeby, S ;
Moe, D .
XENOTRANSPLANTATION, 2002, 9 (04) :260-267