Expression of Egr-1 in late stage emphysema.

The transcription factor early growth response (Egr)-1 is an immediate-early gene product rapidly and transiently expressed after acute tissue injury. In contrast, in this report we demonstrate that lung tissue from patients undergoing lung reduction surgery for advanced emphysema, without clinical or anatomical evidence of acute infection, displays a selective and apparently sustained increase in Egr-1 transcripts and antigen, compared with a broad survey of other genes, including the transcription factor Sp1, whose levels were not significantly altered. Enhanced Egr-1 expression was especially evident in smooth muscle cells of bronchial and vascular walls, in alveolar macrophages, and some vascular endothelium.

alpha-galactosyl epitopes on glycoproteins of porcine renal extracellular matrix.

Background: The pig is the donor animal of choice for human xenotransplantation. In the most relevant pig-to-baboon model, pig organs transplanted into baboons are hyperacutely rejected by natural xenoantibodies, which mainly bind to alpha-galactosyl (alphaGal) epitopes expressed at the surface of endothelial cells. Recent advances in controlling hyperacute rejection have led to improved survival of these xenografts, and it is now important to identify alphaGal binding sites in other cells and tissues that may be subject to immunologic attack.

Interaction of baboon anti-alpha-galactosyl antibody with pig tissues.

As barriers to xenotransplantation are surmounted, such as suppression of hyperacute rejection allowing improved graft survival, it becomes important to define longer-term host-xenograft interactions. To this end we have prepared in baboons high titer anti-alpha-Galactosyl (alphaGal) and anti-porcine aortic endothelial cell antibodies, similar to human natural xenoantibodies and reactive with epitopes of thyroglobulin, laminin, and heparan sulfate proteoglycans. When injected into pigs with a protocol similar to that used in the rat to show the nephritogenic potential of heterologous anti-laminin and anti-heparan sulfate proteoglycan antibodies, baboon immunoglobulins bound first to renal vascular endothelium, and later to interstitial cells, especially fibroblasts and macrophages, and to antigens in basement membranes and extracellular matrix, where they colocalized with laminin- and heparan sulfate proteoglycan-antibodies, and with bound Griffonia simplicifolia B4.

Alpha-galactosyl antibody redistributes alpha-galactosyl at the surface of pig blood and endothelial cells.

The interaction of antibodies with cell surface antigens may induce redistribution of immune complexes, followed by antigen depletion, with increased resistance to injurious effect of antibody and complement (antigenic modulation). Human natural antibodies to Gal alpha 1,3Gal beta 1,4GlcNAc-R (alpha Gal) epitopes expressed at the surface of pig cells are a major obstacle to xenotransplantation. Recent studies have shown that these antibodies do not modulate alpha Gal, but the morphological consequences of the antigen-antibody interaction are unknown.

Membranous glomerulonephritis induced in the pig by antibody to angiotensin-converting enzyme: considerations on its relevance to the pathogenesis of human idiopathic membranous glomerulonephritis.

In the course of studies on the humoral consequences of swine to primate xenotransplantation, the investigators induced formation of glomerular subepithelial immune deposits and tubular lesions in pigs injected with heterologous antibody to angiotensin-converting enzyme. This study describes the morphology of the lesions, discusses their mechanism, explains their relevance for understanding the pathogenesis of human idiopathic membranous glomerulonephritis, and proposes future directions for investigations.