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Long-term success in xenotransplantation is currently hampered by acute vascular rejection. The inciting cause of acute vascular rejection is not yet known; however, a variety of observations suggest that the humoral immune response of the recipient against the donor may be involved in the pathogenesis of this process. Using a pig-to-baboon heterotopic cardiac transplant model, we examined the role of antibodies in the development of acute vascular rejection. After transplantation into baboons, hearts from transgenic pigs expressing human decay-accelerating factor and CD59 underwent acute vascular rejection leading to graft failure within 5 d; the histology was characterized by endothelial injury and fibrin thrombi. Hearts from the transgenic pigs transplanted into baboons whose circulating antibodies were depleted using antiimmunoglobulin columns (Therasorb, Unterschleisshein, Germany) did not undergo acute vascular rejection in five of six cases. Biopsies from the xenotransplants in Ig-depleted baboons revealed little or no IgM or IgG, and no histologic evidence of acute vascular rejection in the five cases. Complement activity in the baboons was within the normal range during the period of xenograft survival. In one case, acute vascular rejection of a xenotransplant occurred in a baboon in which the level of antidonor antibody rose after Ig depletion was discontinued. This study provides evidence that antibodies play a significant role in the pathogenesis of acute vascular rejection, and suggests that acute vascular rejection might be prevented or treated by therapies aimed at the humoral immune response to porcine antigens. (

A recently improved understanding of gut immunity has merged with current thinking in biological and medical science, pointing to an apparent function of the mammalian cecal appendix as a safe‐house for symbiotic gut microbes, preserving the flora during times of gastrointestinal infection in societies without modern medicine. This function is potentially a selective force for the evolution and maintenance of the appendix, and provides an impetus for reassessment of the evolution of the appendix. A comparative anatomical approach reveals three apparent morphotypes of the cecal appendix, as well as appendix‐like structures in some species that lack a true cecal appendix. Cladistic analyses indicate that the appendix has evolved independently at least twice (at least once in diprotodont marsupials and at least once in Euarchontoglires), shows a highly significant (P < 0.0001) phylogenetic signal in its distribution, and has been maintained in mammalian evolution for 80 million years or longer.

It is critical, both for the host and for the long-term benefit of the bacteria that colonize the gut, that bacterial overgrowth with subsequent bacterial translocation, which may lead to sepsis and death of the host, be avoided. Secretory IgA (sIgA) is known to be a key factor in this process, agglutinating bacteria and preventing their translocation in a process termed 'immune exclusion'. To determine whether human sIgA might facilitate the growth of normal enteric bacteria under some conditions, the growth of human enteric bacteria on cultured, fixed human epithelial cells was evaluated in the presence of sIgA or various other proteins. Human sIgA was found to facilitate biofilm formation by normal human gut flora and by Escherichia coli on cultured human epithelial cell surfaces under conditions in which non-adherent bacteria were repeatedly washed away. In addition, the presence of sIgA resulted in a 64% increase in adherence of E. coli to live cultured epithelial cells over a 45-min period. Mucin, another defence factor thought to play a key role in immune exclusion, was found to facilitate biofilm formation by E. coli. Our findings suggest that sIgA may contribute to biofilm formation in the gut.

These results demonstrate that anti-Galalpha1-3Gal antibodies cause acute vascular rejection and suggest that depletion of these antibodies leads to accommodation of the donor cardiac xenograft and could supply an important model for additional study.

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Sodium dodecyl sulfate (SDS) is used more often than any other detergent as an excellent denaturing or "unfolding" detergent. However, formation of ordered structure (alpha-helix or beta-sheet) in certain peptides is known to be induced by interaction with SDS micelles. The SDS-induced structures formed by these peptides are amphiphilic, having both a hydrophobic and a hydrophilic face. Previous work in this area has revealed that SDS induces helical folding in a wide variety of non-helical proteins. Here, we describe the interaction of several structurally unrelated proteins with SDS micelles and the correlation of these structures to helical amphiphilic regions present in the primary sequence. It is likely that the ability of native nonordered protein structures to form induced amphiphilic ordered structures is rather common.