Reactivity of Human Natural Antibodies to Endothelial Cells From Gal??(1,3)Gal-Deficient Pigs

Baumann, Bettina C.; Stüssi, Georg; Huggel, Katja; Rieben, Robert; Seebach, Jörg Dieter

doi:10.1097/01.tp.0000250478.00567.e5

Cited by 69 publications

(75 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other endogenous factors, including MD-2 and the lipoprotein receptor, may be required for interaction with TLR4 (18,25). We have reported that the sulfated polysaccharide carrageenan, which has the unusual ␣-1,3-galactosidic link that is the epitope for the anti-Gal antibody (2,12), is recognized by TLR4 and induces an innate immune response mediated by Bcl10, as well as an ROS-mediated inflammatory response (3,4). The O-antigen of enteropathogenic Escherichia coli O86 and O127 appears to have some similarly configured linkages between galactose and N-acetylgalactosamine residues (10), suggesting a possible relationship to pathogenicity.…”

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide activates NF-κB by TLR4-Bcl10-dependent and independent pathways in colonic epithelial cells

Bhattacharyya¹,

Dudeja²,

Tobacman³

2008

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide activates NF-κB by TLR4-Bcl10-dependent and independent pathways in colonic epithelial cells

Bhattacharyya¹,

Dudeja²,

Tobacman³

2008

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

show abstract

“…The latter contributes to the confusion about the role of IgG (subclasses) versus IgM Abs in humoral rejection. To resolve these problems, we utilized a recently established semiquantitative flow cytometry-based method, ABO fluorescence-activated cell sorting (ABO-FACS), to measure anti-A/B and antiporcine IgM/IgG Ab serum levels prior to, and after, a living-donor ABO-incompatible kidney transplantation (14,15).…”

mentioning

confidence: 99%

Flow Cytometric Measurement of ABO Antibodies in ABO-Incompatible Living Donor Kidney Transplantation

Yung¹,

Valli²,

Starke³

et al. 2007

Transplantation

Self Cite

View full text Add to dashboard Cite

Due to different detection methods, a comparison of anti-A/B antibody (Ab) levels among transplantation centers after living donor ABO-incompatible kidney transplantation is problematic. In the present study, anti-A/B Ab levels were determined prior to, and after, blood group A-to-O kidney transplantation using a recently established semiquantitative flow cytometry-based method, ABO fluorescence-activated cell sorting (ABO-FACS), and compared with standard agglutination titers and indirect antiglobulin testing. Pretransplant agglutination titers were reduced from 1:64 to 1:4, by a total of 14 Glycosorb A column immunoadsorptions (IADSs). Compared with the agglutination titers, antidonor immunoglobulin (Ig) M ABO-FACS mean fluorescence intensity ratios (MFIRs) decreased faster and remained low. No difference was observed using donor type or third-party A red blood cells (RBCs) for the ABO-FACS. Glycosorb A columns were not specific, also reducing anti-B and antiporcine IgM levels, which was confirmed by detecting anti-A/B and antiporcine Abs in the column eluates. In conclusion, analysis of pre- and posttransplant Abs from ABO-incompatible kidney transplant recipients by ABO-FACS allows a better understanding of Ab kinetics, which may improve the design of future IADS protocols.

show abstract

“…The biological reactivity of CGN may be attributable to some extent to its activation of a pathway of innate immunity, due to CGN's unique structure that includes the immunogenic gal(α-1,3)gal epitope [1,2]. Of mammals, only humans and Old World apes lack the alpha-1,3-galactosyl transferase enzyme that is required to form the alpha-1,3-galactosidic linkage, recognized by the anti-Gal antibody [3,4].…”

Section: Introductionmentioning

confidence: 99%

Carrageenan-induced NFκB activation depends on distinct pathways mediated by reactive oxygen species and Hsp27 or by Bcl10

Bhattacharyya

Dudeja

Tobacman

2008

Biochimica et Biophysica Acta (BBA) - General Subjects

View full text Add to dashboard Cite

Carrageenans are highly sulfated polysaccharides that are widely used as food additives due to their ability to improve food texture. They are also widely recognized for their ability to induce inflammation in animal models of colitis. Recently, we reported that carrageenan (CGN) activated a pathway of innate immunity in human colonic epithelial cells mediated by Bcl10 (B-cell CLL/ lymphoma 10). However, increases in phospho-IκBα and Interleukin-8 (IL-8) were not completely inhibited by silencing Bcl10, suggesting that CGN also influenced another mechanism, or mechanisms, of inflammation. In this report, we demonstrate that CGN increases production of reactive oxygen species (ROS) in human colonic epithelial cells. The combination of ROS quenching by the free radical scavenger Tempol and of Bcl10 silencing by siRNA completely inhibited the CGN-induced increases in nuclear NFκB (p65), phospho-IκBα, and secretion of IL-8. The CGN-induced increase in ROS was associated with declines in phosphorylation of MAPK 12 (p38γ), MAPK 13 (p38δ), and heat-shock protein (Hsp) 27. The CGN-induced decline in phospho-Hsp27 was reversed by co-administration of Tempol (100nM), but unaffected by silencing Bcl10. Since Hsp27 phosphorylation is inversely associated with phosphorylation of the IκBα kinase (IKK) signalosome, CGN exposure appears to affect the IKK signalosome by both the catalytic component, mediated by ROS-phospho-Hsp27, and the regulatory component, mediated by Bcl10 interaction with IKKγ (Nemo). Hence, the CGN-activated inflammatory cascades related to innate immunity and to generation of ROS may be integrated at the level of the IKK signalosome.

show abstract

Reactivity of Human Natural Antibodies to Endothelial Cells From Gal??(1,3)Gal-Deficient Pigs

Abstract: The generation of Gal-deficient pigs has overcome hyperacute anti-Gal-mediated xenograft rejection in nonhuman primates. Non-Gal anti-porcine NAb represent a potentially relevant immunological hurdle in a subgroup of individuals by inducing endothelial damage in xenografts.

Cited by 69 publications

References 40 publications

Lipopolysaccharide activates NF-κB by TLR4-Bcl10-dependent and independent pathways in colonic epithelial cells

Lipopolysaccharide activates NF-κB by TLR4-Bcl10-dependent and independent pathways in colonic epithelial cells

Flow Cytometric Measurement of ABO Antibodies in ABO-Incompatible Living Donor Kidney Transplantation

Carrageenan-induced NFκB activation depends on distinct pathways mediated by reactive oxygen species and Hsp27 or by Bcl10

Contact Info

Product

Resources

About