Evidence That Long-Term Survival of Concordant Xenografts Is Achieved by Inhibition of Antispecies Antibody Production

Hasan, Rimsha; Bogaerde, J. B. Van Den; Wallwork, J.; White, David J.

doi:10.1097/00007890-199209000-00004

Cited by 76 publications

(32 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Delayed xenograft rejection (DXR) 3 is an intermediate form of graft rejection characterized by overwhelming monocyte and NK cell infiltration, Ab deposition along the endothelium, endothelial cell activation, thrombosis, and eventually graft loss (1,2). Many components of the innate and acquired immune systems, including xenoreactive Abs, complement, coagulation factors, monocytes, and NK cells, can act independently or in concert to effect xenograft damage, but the mechanisms that initiate DXR are poorly understood (3)(4)(5)(6)(7)(8). Since DXR represents the most important immunological hurdle preventing routine use of xenografts for the treatment of end-organ failure, additional studies are necessary to elucidate the mechanisms underlying DXR.…”

mentioning

confidence: 99%

Monocyte Adhesion to Xenogeneic Endothelium during Laminar Flow Is Dependent on α-Gal-Mediated Monocyte Activation

Peterson

Jin

Hyduk

et al. 2005

The Journal of Immunology

View full text Add to dashboard Cite

Monocytes are the predominant inflammatory cell recruited to xenografts and participate in delayed xenograft rejection. In contrast to allogeneic leukocytes that require up-regulation of endothelial adhesion molecules to adhere and emigrate into effector tissues, we demonstrate that human monocytes adhere rapidly to unstimulated xenogeneic endothelial cells. The major xenoantigen galactoseα(1,3)galactoseβ(1,4)GlcNAc-R (α-gal) is abundantly expressed on xenogeneic endothelium. We have identified a putative receptor for α-gal on human monocytes that is a member of the C-type family of lectin receptors. Monocyte arrest under physiological flow conditions is regulated by α-gal, because cleavage or blockade results in a dramatic reduction in monocyte adhesion. Recruitment of human monocytes to unactivated xenogeneic endothelial cells requires both α4 and β2 integrins on the monocyte; binding of α-gal to monocytes results in rapid activation of β2, but not α4, integrins. Thus, activation of monocyte β2 integrins by α-gal expressed on xenogeneic endothelium provides a mechanism that may explain the dramatic accumulation of monocytes in vivo.

show abstract

mentioning

confidence: 99%

Monocyte Adhesion to Xenogeneic Endothelium during Laminar Flow Is Dependent on α-Gal-Mediated Monocyte Activation

Peterson

Jin

Hyduk

et al. 2005

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…CyA did not influence IgM Ab production, but it completely inhibited IgG Ab formation, as we and others have previously shown (11,14,38,39). Whereas IgM Abs elicited during sensitization still led to rejection of hamster hearts within 24 h (group 1), addition of CVF to the CyA treatment induced long-term survival and accommodation of hearts (7/8) in those presensitized recipients having only IgM anti-graft Abs (group 2).…”

Section: Graft Survival In Rats Presensitized In the Presence Of Cyamentioning

confidence: 56%

“…We and others have previously shown that rats do not have sufficient preformed anti-hamster Abs to provoke hyperacute rejection of hamster hearts (11)(12)(13)(14)37). After sensitization (Table I), rats hyperacutely (within minutes) reject hamster hearts (group 1).…”

Section: Survival Of Hamster Hearts In Presensitized Ratsmentioning

confidence: 95%

“…Although there are also IgM and IgG EXA that lead to DXR in concordant xenotransplantation such as hamster to rat, treatment of the recipient with a number of immunosuppressive protocols that suppress IgG EXA production induces long-term survival of the graft (11)(12)(13)(14). We have shown that treatment with just two doses of cobra venom factor (CVF) plus daily cyclosporin A (CyA) blocks complement activation for a few days and IgG synthesis permanently, respectively, and results in long-term survival of the grafts (15,16).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Long-Term Survival of Hamster Hearts in Presensitized Rats

Lin

Soares

Sato

et al. 2000

The Journal of Immunology

View full text Add to dashboard Cite

We transplanted hamster hearts into rats that had been sensitized to hamster cardiac grafts 5 days earlier as a model for discordant xenotransplantation. Sensitized rats had high serum levels of elicited anti-donor IgM and IgG that caused hyperacute rejection. Transient complement inhibition with cobra venom factor (CVF) plus daily and continuing cyclosporin A (CyA) prevented hyperacute rejection. However, grafts underwent delayed xenograft rejection (DXR). DXR involved IgG and associated Ab-dependent cell-mediated rejection, because depletion of IgG or Ab-dependent cell-mediated rejection-associated effector cells prolonged graft survival and the serum-mediated Ab-dependent cell-mediated cytotoxicity in vitro. Blood exchange in combination with CVF/CyA treatment dramatically decreased the level of preexisting Abs, but DXR still occurred in association with the return of Abs. Splenectomy and cyclophosphamide acted synergistically to delay Ab return, and when combined with blood exchange/CVF/CyA facilitated long-term survival of grafts. These grafts survived in the presence of anti-donor IgM, IgG, and complement that precipitated rejection of naive hearts, indicating that accommodation (survival in the presence of anti-graft Abs and complement) had occurred. We attribute the long-term survival to the removal of preexisting anti-donor Abs and therapy that attenuated the rate of Ab return. Under such conditions, the surviving hearts showed expression in endothelial cells and smooth muscle cells of protective genes and an intragraft Th2 immune response. Th2 responses and protective genes are associated with resistance to IgM- and IgG-mediated, complement-dependent and -independent forms of rejection.

show abstract

“…Because these xenografts after transplantation elicit a strong humoral response and are rejected within a few days, these models were considered until the last few years to be moderately difficult [1][2][3][4][5][6][7][8][9][10], more so than the sheep-to-goat combination of Perper and Najarian [n] or the wolf-to-dog model of Hammer et al [12].…”

Section: Introductionmentioning

confidence: 99%

Use of Tacrolimus (FK506) and Antimetabolites as Immunosuppressants for Xenotransplantation Across Closely Related Rodent Species

Valdivia¹,

Murase²,

Rao³

et al. 1997

Xenotransplantation

View full text Add to dashboard Cite

Evidence That Long-Term Survival of Concordant Xenografts Is Achieved by Inhibition of Antispecies Antibody Production

Cited by 76 publications

References 0 publications

Monocyte Adhesion to Xenogeneic Endothelium during Laminar Flow Is Dependent on α-Gal-Mediated Monocyte Activation

Monocyte Adhesion to Xenogeneic Endothelium during Laminar Flow Is Dependent on α-Gal-Mediated Monocyte Activation

Long-Term Survival of Hamster Hearts in Presensitized Rats

Use of Tacrolimus (FK506) and Antimetabolites as Immunosuppressants for Xenotransplantation Across Closely Related Rodent Species

Contact Info

Product

Resources

About