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Biomedical subjects

F P Sanfilippo

Publications and source records attributed to F P Sanfilippo.

At least 19 recordsLinked to original sources

Expression of a copper-containing amine oxidase by human ciliary body.

PURPOSE: To examine the molecular structure and ultrastructural distribution of a novel amine oxidase in human ciliary body. METHODS: Human ciliary bodies were solubilized with a nonionic detergent. The solubilized material was subjected to affinity chromatography with 2B4.14.1, a monoclonal antibody which recognizes a family of ciliary body glycoproteins. Proteins eluted from the affinity column were further separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Peptides produced from a 2B4.14. 1-reactive protein with an approximate molecular weight of 100 kDa were analyzed by Edman degradation. The protein thus identified was further examined by Western blotting and immunoelectron microscopy with anti-peptide antisera. RESULTS: Peptide sequences from the 100 kDa ciliary body protein were identical to the predicted protein sequence of an amine oxidase identified recently in a human placental cDNA library. The identity of the ciliary body protein was confirmed by Western blotting with rabbit antiserum generated against the predicted carboxy-terminal peptide of human placenta amine oxidase. Western blotting under nonreducing conditions and following glycosidase digestion indicated that the native enzyme is a disulfide-linked homodimer with multiple N-linked oligosaccharide side chains. By immunoelectron microscopy, the ciliary body amine oxidase was localized to the plasma membranes of inner epithelial cells. CONCLUSIONS: Human placenta amine oxidase is present on the plasma membranes of ciliary body inner epithelial cells. This finding provides a potential explanation for amine oxidase enzyme activity detected in previous studies of anterior segment tissues. Though the functional role of human placenta amine oxidase in the eye is unclear, it may contribute to the production of H2O2 in aqueous humor.

Aged↗

Regional organ procurement (ROP) trays in renal allograft distribution and outcome.

ROP trays containing patient serum samples and distributed by the South-Eastern Organ Procurement Foundation (SEOPF) were instituted to increase the likelihood of transplanting potential renal recipients who are highly sensitized to HLA antigens. This study examines kidney distribution and transplant outcome to assess equitable placement and clinical function post transplant with and without the use of ROP trays. Data were collected over a 26-month period on the distribution of kidneys from 328 consecutive SEOPF donors from whom at least 1 kidney was procured. Shared kidneys were placed via the UNOS and SEOPF-variance computer match programs. Of 656 kidneys, 596 were placed into 582 recipients; 60 were not used. ROP trays were used in placement of 492 kidneys and were not used for placement of 104 kidneys. Outcome was determined for 435 kidneys transplanted into SEOPF recipients. Only 33 (6.9%) recipients with ROP tray use and 10 (9.8%) without were sensitized to HLA. A 10% increase in placement to the originally intended recipient was seen with ROP tray usage over kidneys placed without ROP tray use (p < or = 0.025). Recipients matched using ROP tray data averaged 29 positions higher on the match printout. There was no difference in tray use regarding placement of kidneys within or outside the donor's local UNOS region, nor was there a difference in mean HLA match of transplant pairs with and without ROP tray use, 3.2 and 3.1 antigens, respectively. Cold ischemia time was similar, 22.9 and 23.6 h, respectively, for kidneys placed with and without ROP trays. At post-transplant discharge, there were no differences in patient status, graft failure, rejection treatment, dialysis need, or urine output whether or not ROP trays were used. Significantly, however, plasma creatinine at discharge and at 12 months was lower for those placed with ROP trays (2.5 mg/dl and 1.7 mg/dl) vs (3.1 mg/dl and 1.9 mg/dl), respectively. During this time period, all kidneys transplanted with use of ROP trays functioned as well or better than those transplanted without ROP tray placement. Thus, the use of ROP trays appeared to have a beneficial effect in getting more recipients of higher priority transplanted with equivalent, if not better, graft function.

Cold Temperature↗

Rejection of kidney allografts by MHC class I-deficient mice.

To evaluate the requirement for CD8+ T cells in kidney transplant rejection, we studied class I-deficient (class I-) mice that had received vascularized renal allografts. Because of the absence of MHC class I expression, these mice are grossly deficient in CD4-CD8+ alpha beta TCR+ cells. Despite the deficiency of CD8+ T cells in naive class I- mice, kidney allografts transplanted into class I- recipients developed significant reductions in renal blood flow and glomerular filtration rate to levels comparable to allograft controls. This functional deterioration was associated with histologic changes consistent with cellular rejection. There were no significant differences in the pattern, severity, or phenotypic character of the cellular infiltrate in allografts transplanted into class I- recipients compared to controls. In fact, substantial numbers of CD8+ T cells were present in these allografts, and the intensity and pattern of anti-CD8 staining was not different from controls. Virtually all of the CD8+ cells in the kidney grafts were class I- and CD4- and co-expressed CD8 alpha and beta chains; the majority were alpha beta TCR+. The CD8+ infiltrating cells were cytotoxic to donor targets but also exhibited activity against class I+ cells bearing self-MHC. Despite the marked CD8+ T cell infiltration of grafts, CD8+ T cells could not be detected by flow cytometry in freshly isolated splenocytes from the class I- recipients of allografts. High levels of circulating anti-class I antibodies were present in the serum of class I- recipients of kidney allografts, and these antibodies had unusual specificity in that they appeared to recognize framework epitopes of MHC class I. Thus, class I- mice readily reject kidney allografts. Although the number of CD8+ alloreactive precursors is substantially reduced in class mice, and their specificities are atypical, the pattern and character of the intra-graft CD8+ cellular response is not significantly altered. Thus, factors unrelated to precursor frequency determine the dimension of the intra-graft CD8+ response. Such factors might include cellular and/or biochemical properties of microenvironment within the graft.

Animals↗

Immunohistochemical analysis of the pathogenesis of posterior polymorphous dystrophy.

The pathogenesis of posterior polymorphous dystrophy was analyzed by immunohistologic methods. Sections of corneal buttons from two patients undergoing transplantation owing to posterior polymorphous dystrophy were stained with 2B4.14.1, a monoclonal antibody that reacts with human corneal endothelium, and with a cocktail of antihuman cytokeratin monoclonal antibodies that do not react with normal corneal endothelium. Single-stained sections revealed a variegated, intermittent staining pattern of antibody reactive and nonreactive cells. Double-stained sections revealed some cells that stained with only one of the antibodies and many cells that stained with both antibodies. The presence of cells staining positively for both 2B4.14.1 antigen and cytokeratins supports the hypothesis that the cytokeratin-expressing epithelial-like cells found in corneas with posterior polymorphous dystrophy arise via a metaplastic process in which the phenotype of endothelial cells becomes progressively abnormal.

Adult↗

Identification of selective immunoglobulin a deficiency by renal biopsy.

We report three cases of selective immunoglobulin A (IgA) deficiency in which lack of direct immunofluorescent staining for IgA on renal biopsy specimens contributed to the diagnosis. In two patients, one with systemic lupus erythematosus and the other having asthma with nephrotic syndrome, the diagnosis of IgA deficiency was suggested by the complete absence of IgA on the renal biopsy. In the third patient, a renal transplant recipient, initial biopsies demonstrated donor-derived IgA, which disappeared on subsequent biopsies. The diagnosis of IgA deficiency was confirmed in all three patients by serologic quantification of IgA.

Adolescent↗

Differential expression of CD43 (leukosialin, sialophorin) by mononuclear phagocyte populations.

CD43 is a hematopoietic cell antigen whose distribution includes T lymphocytes, plasma cells, neutrophils, and platelets. Although it has been detected on peripheral blood monocytes, its expression by other mononuclear phagocytes has not been well documented. Possible changes in monocyte/macrophage CD43 expression in response to inflammation are also poorly defined. To examine these questions, the expression of CD43 by rat peripheral blood monocytes and both resident and elicited peritoneal macrophages was examined. By flow cytometry with two anti-CD43 monoclonal antibodies, blood monocytes were found to express large amounts of surface CD43, whereas surface CD43 expression by resident peritoneal macrophages was negligible. Peritoneal macrophage populations elicited by intraperitoneal injection of thioglycollate were uniformly positive for surface CD43, although the level of expression was lower than that found on monocytes. By labeling resident macrophages with a fluorescent tracer dye, this phenotypic shift was found to reflect an influx of CD43-positive elicited macrophages coupled with a disappearance of CD43-negative resident cells. Evidence from both flow cytometry and Western blotting studies suggests that the CD43 expressed by elicited peritoneal macrophages is less heavily sialylated than that expressed by blood monocytes. These findings, coupled with recent evidence that CD43 influences cellular adhesion, indicate that differential expression of CD43 may play a role in monocyte/macrophage trafficking.

Animals↗

Histopathologic features of rejecting orthotopic corneal xenografts.

Discordant xenogeneic Hartley guinea pig corneal buttons were transplanted orthotopically to either naive or pre-immune Lewis rats. Recipients were sacrificed serially and grafts were immediately frozen and subsequently examined using standard immunohistologic techniques. Corneal xenografts remained clear in naive recipients for 7 days, at which point they rapidly became opaque and edematous. In pre-immunized recipients, corneal xenografts were rejected much more quickly, becoming opaque and edematous by day 3 post-transplantation. Histologic examination of grafts revealed severe stromal edema and diffuse inflammatory cell infiltrates composed of mononuclear cells and neutrophils. Infiltrates were present as early as day 2 in xenografts from both presensitized and naive recipients. The infiltrates were densest in the posterior half of the grafts with fewer cells penetrating into the epithelium. Immunoperoxidase staining confirmed the presence of OX-19+ T cells as well as a substantial infiltrate of OX-42+ neutrophils/macrophages. Additionally, IgG was deposited throughout the grafts in a diffuse manner. Deposition of IgG was accelerated in presensitized recipients, with intense staining of the entire graft detected by day 2. Examination of the rejected grafts suggests that rejection occurs via mechanisms similar to those seen in corneal allografts. This, in turn, implies corneal xenografts may be amenable to standard immunosuppressive regimens.

Animals↗

Characterization of a novel family of ciliary body glycoproteins.

PURPOSE: To isolate and characterize ciliary body epithelial antigens reactive with a monoclonal antibody, 2B4.14.1. METHODS: A mouse monoclonal antibody generated against human corneal endothelium, 2B4.14.1 reacts with nonpigmented epithelium of human and guinea pig ciliary bodies. The ciliary body proteins reactive with 2B4.14.1 were identified by Western blotting and were partially purified by affinity chromatography with 2B4.14.1 coupled to a solid support matrix. Carbohydrate components of the antigenic molecules were analyzed by lectin chromatography and by digestion with the enzymes N-glycosidase F and endoglycosidase F. The cellular and subcellular distribution of the antigens was examined by immunoperoxidase staining and by immunoelectron microscopy of ultracryotome sections of ciliary body. RESULTS: 2B4.14.1 reacted with families of guinea pig and human ciliary body glycoproteins with estimated molecular weights ranging from 250 to 325 kD. In Western blots of samples reduced before electrophoresis, the high molecular weight bands were replaced by weakly reactive bands at 115 to 130 and 210 kD, indicating that the 2B4.14.1 ligands have disulfide bonds. 2B4.14.1 ligands from both guinea pig and human ciliary body were bound by immobilized lectins, including concanavalin A, Datura stramonium lectin, and Lens culinaris hemagglutinin, which recognize components of N-linked oligosaccharides. Guinea pig ciliary body antigens digested with N-glycosidase F and endoglycosidase F failed to react with 2B4.14.1 in Western blots, confirming the presence of N-linked oligosaccharide chains and indicating that they form an integral part of the 2B4.14.1-reactive antigenic site. Molecular weight shifts of glycosidase-digested antigens were consistent with the presence of two to four N-linked oligosaccharide units. In immunoperoxidase-stained sections of guinea pig and human ciliary body, 2B4.14.1 reacted primarily with nonpigmented epithelial cells. Staining of guinea pig epithelial cells was fairly uniform; staining of human epithelial cells was concentrated on the basal surface. By immunoelectron microscopy, a majority of the 2B4.14.1 antigenic reactivity was localized immediately external to the nonpigmented epithelial cell plasma membrane. CONCLUSIONS: 2B4.14.1 reacts with a novel family of high molecular weight glycoproteins associated with the nonpigmented epithelial cell surface in guinea pig and human ciliary body.

Aged↗

Characterization of human anti-porcine "natural antibodies" recovered from ex vivo perfused hearts--predominance of IgM and IgG2.

Hyperacute rejection is a major obstacle to successful transplantation of vascularized xenogeneic organs and is believed to be mediated at least in part by performed xenoreactive "natural antibodies" (NAb). In this study, human NAb that could be involved in hyperacute rejection of pig heart xenografts were identified and characterized using an ex vivo model in which pig hearts were perfused with whole blood from individual human or pig donors. This ex vivo perfusion model allows for the continuous monitoring of physiologic parameters of cardiac function as well as sequential sampling of tissue and blood. Pig hearts perfused with allogeneic pig blood maintained normal function for at least 4 hr, whereas those perfused with xenogeneic AB+ human blood never achieved normal function and rejected completely after 30 min. In three separate experiments involving different human blood donors and pig hearts, sequential samples of perfused blood revealed a progressive depletion of anti-porcine NAb. Samples of all three rejected cardiac xenografts were homogenized, and the specifically bound human anti-porcine antibodies were eluted with citric acid. The eluted antibodies were enriched approximately 50-120-fold for anti-porcine reactivity compared with serum from the corresponding donor. Eluates contained NAb of predominantly IgM and IgG2 isotypes. Immunofluorescence histology confirmed the deposition of IgM and IgG2 but not other IgG subclasses in the rejected pig hearts. Since IgG2 utilized predominantly in response to bacterial polysaccharide antigens, our findings are consistent with the possibility that some NAb arise via crossreactivity with microbial antigens and are predominantly directed against carbohydrate rather than protein antigens.

Animals↗

Immunosuppressive therapy as a determinant of transplantation outcomes.

Although surgical proficiency is essential to the immediate outcome of transplantation, long-term success depends upon how adequately the transplantation recipient is managed. Immunosuppression, the most critical aspect of after care, is subject to wide variation. In January 1990, a survey was sent to the directors of all transplant programs in the United States performing one or more kidney, heart, liver, heart-lung, or pancreas transplant in 1988. Detailed data were obtained on both the drugs and methods used for induction and maintenance immunosuppression, as well as the treatment of rejection. Each program director was asked to rank each immunosuppressive approach according to its perceived impact on patient outcomes. Over 85% of all eligible program directors completed the survey. There is no evidence of survey respondent bias. The use of polyclonal and monoclonal agents for induction immunosuppression was favored most by pancreas program directors (72-76%). These agents were least preferred by liver transplant programs (35-37%). About half of kidney, heart, and heart-lung program directors preferred these agents. Triple-drug therapy consisting of CsA, PRED, and AZA was considered the most preferable maintenance protocol for all transplants (i.e., kidney, 89%; heart, 94%; liver, 88%; heart-lung, 86%; pancreas, 96%). Either i.v. steroids or OKT3 were regarded as the preferred approaches for the treatment of acute or resistant rejection. Finally, the acceptability of outpatient treatment of rejection varied by transplant type (i.e., kidney, 9%; heart, 58%; liver, 5%; heart-lung, 29%; pancreas, 8%). Although there are similarities in the ratings of various aspects of immunosuppressive therapy, there are important differences. This information is critical to anticipate the implications of new immunosuppressive agents and to evaluate changes in the use of existing drugs and therapeutic approaches.

Data Collection↗

Alterations in renal interleukin-1 production during kidney transplant rejection in the rat. The effects of high-dose methylprednisolone.

To characterize the role of interleukin-1 in renal allograft rejection, we examined the temporal relationship of IL-1 production to changes in renal function and histology in a rat kidney transplantation model. In rat renal allografts, both glomerular filtration rate and renal plasma flow (RPF) fell progressively from days 4 through 6 following transplantation. The reduction in allograft function was accompanied by histologic changes consistent with rejection and enhanced steady-state levels of IL-1 beta mRNA measured by Northern blot. This increase in IL-1 beta mRNA levels was associated with a forty-fold increase in IL-1 bioactivity in eluates of kidney allografts compared with isografts. In rejecting allografts, these changes also coincided with increased production of thromboxane B2 (TxB2) by the graft. To attempt to modify IL-1 production in the transplanted kidney, a separate group of animals with renal allografts were treated with 80 mg/kg/day of methylprednisolone for 6 days. GFR in MP-treated animals was significantly preserved compared with vehicle-treated animals. However, similar histologic manifestations of rejection were found in both groups. Although IL-1 beta mRNA levels in the kidney were not changed with MP treatment, renal IL-1 bioactivity was reduced four-fold in animals that received MP compared with controls. Thus, IL-1 beta gene expression and IL-1 protein production are stimulated in rejecting kidney transplants. MP administration improves allograft function and inhibits IL-1 production, apparently at a post-transcriptional level. We hypothesize that overproduction of IL-1 during kidney transplant rejection may promote allograft dysfunction and injury. Some of the beneficial effects of corticosteroids in acute rejection may be mediated through inhibition of IL-1 release within the allograft.

Animals↗

Characteristics of corneal xenograft rejection in a discordant species combination.

PURPOSE: To characterize the fate of Lewis rat corneas transplanted to Hartley guinea pigs. METHODS: Full-thickness Lewis rat corneal buttons were grafted orthotopically to Hartley guinea pigs (xenografts), ACI rats (allografts), or Lewis rats (isografts). Two panels of recipients were presensitized with xenogeneic skin grafts or allogeneic skin grafts. Serum samples were collected pre- and post-transplant and analyzed by flow cytometry and indirect immunofluorescence. RESULTS: Unlike vascularized xenografts that reject within 30 min, corneal xenografts had a mean survival time of 8 days. Presensitization with guinea pig skin grafts increased recipient IgM and IgG xenoantibody levels, as measured by flow cytometry on guinea pig hematopoietic cells, and significantly accelerated corneal xenograft rejection with a mean survival time of 5 days. Presensitization with allogeneic ACI skin grafts had no effect on xenoantibody levels or xenogeneic corneal graft survival. Guinea pig corneas stained by indirect immunofluorescence with normal rat serum exhibited low (1+) but significant binding of IgG and IgM, primarily on epithelium and stroma. Serum from Lewis rats that rejected a corneal xenograft had elevated IgG and IgM xenoantibodies that reacted strongly (4+) with guinea pig cornea and heart. CONCLUSIONS: In the discordant guinea pig-to-rat species combination, donor corneas express xenoantigens; rejection of corneal xenografts stimulates IgM and IgG xenoantibody production; sensitization to xenoantigens can accelerate corneal xenograft rejection; and discordant corneal xenografts, unlike vascularized organs, are not hyperacutely rejected.

Acute Disease↗

Factors affecting the waiting time of cadaveric kidney transplant candidates in the United States.

UNLABELLED: OBJECTIVE--To evaluate the relative impact of various factors that could account for differences in waiting time of cadaveric kidney transplant candidates (eg, black and sensitized patients). DESIGN: --A cohort study using multivariate analyses to identify associations between 36 patient, donor, and center factors with waiting time for all US cadaveric kidney transplant candidates listed between October 1, 1987, and June 30, 1990. SETTING--All US kidney transplant centers. PATIENTS--The study included 23,468 cadaveric renal transplant candidates on active waiting status. RESULTS--The patient characteristics most significantly associated with increased waiting time (adjusted for all other variables) were immunologic and included presensitization to HLA antigens, O or B blood type, candidacy for a repeat transplantation, and expression of rare HLA-A or HLA-B antigen phenotypes. Nonimmunologic factors also affected waiting times, which were significantly shorter for patients younger than 15 years vs those aged 15 through 44 years (8.4 vs 12.9 months, respectively; P less than .0001), for those listed at multiple centers vs one center (7.0 vs 13.3 months, respectively; P less than .0001), or for white vs black patients (11.9 vs 15.4 months, respectively; P less than .0001). Local transplant center characteristics associated with a significantly shorter waiting time included a small number of transplantation candidates, a high (greater than 35 per million population) local kidney organ recovery rate, and an approved variance from the Organ Procurement and Transplantation Network allocation algorithm. CONCLUSIONS--The time renal transplant candidates must wait for kidney transplantation is influenced by several factors in addition to those expected due to immunologic reasons of donor incompatibility, the algorithms used for organ distribution, or the effectiveness of local kidney recovery. The impact of these factors should be considered as the current US system for allocating scarce donor organs for kidney transplantation is modified.

Black or African American↗

Duplex Doppler sonography of renal transplants: lack of sensitivity and specificity in establishing pathologic diagnosis.

Recent reports have suggested the value of duplex Doppler sonography in the assessment of renal transplant function. Accurate diagnosis of acute rejection and its distinction from acute tubular necrosis and cyclosporine A toxicity have been claimed. We undertook a combined retrospective and prospective analysis of duplex Doppler examinations performed over a 2-year period to assess the value of such studies in evaluating renal allograft dysfunction. Seventy-seven sonographic examinations were performed on 77 renal transplants. A mean resistive index was calculated from Doppler measurements within main, segmental, and interlobar renal arteries by using the following ratio. peak systolic blood-flow velocity--minimum end-diastolic blood-flow velocity/peak systolic blood-flow velocity Forty-eight Doppler results were correlated with transplant biopsies and 29 with clinical course. Twenty-three episodes of acute allograft rejection were confirmed. When a resistive index of greater than or equal to 0.9 was used to indicate acute rejection, sonography had a sensitivity of only 9% and a specificity of 91% for this diagnosis. In one of eight cases of cyclosporine A toxicity and in three of six examples of acute tubular necrosis, the resistive index was greater than 0.9. In all six instances of chronic rejection, the resistive index was less than 0.84. None of eight patients with evidence of infection had a resistive index greater than 0.9. The resistive index range of 12 normally functioning allografts was 0.57-0.69. Correlation between the resistive index and the severity of arterial and arteriolar changes on biopsy was poor. An increased resistive index of renal transplant blood flow, as measured by duplex Doppler sonography, usually signals pathologic changes in an allograft. However, our data indicate that this test is not as sensitive or specific in identifying the cause of transplant dysfunction as has been suggested previously.

Adolescent↗

Histopathologic and immunochemical features of lattice corneal dystrophy type III.

We examined seven corneas from five patients with a new form of lattice corneal dystrophy (designated lattice corneal dystrophy type III) by light and electron microscopy. Numerous amyloid deposits were scattered throughout the corneal stroma, some of which were much larger than those usually observed in either lattice corneal dystrophy type I or II; these were located predominantly midway between the epithelium and the endothelium. Image analysis disclosed that the cross-sectional size of the large stromal amyloid deposits was significantly greater than those in age-matched patients with lattice corneal dystrophy type I. All patients had a discontinuous band of amyloid (15 to 25 micron wide) in the superficial stroma beneath Bowman's layer, which usually had only one or two small disruptions. Descemet's membrane and the endothelium were normal. The stromal deposits, which were composed of 10-nm diameter fibrils typical of amyloid, stained positively with Congo red after the histologic sections were pretreated with dilute potassium permanganate. Immunohistochemical studies on formalin-fixed, paraffin-embedded tissue indicated that only some deposits reacted weakly with antibodies to amyloid protein AA. The deposits stained positively with antibodies to protein AP and negatively with antibodies to kappa and lambda immunoglobulin light chains.

Amyloid↗

Lymphocytotoxicity crossmatch proficiency testing among regional transplant centers.

During an eight and a half-year period (1976-1984), 408 combinations of different cells and sera involving 12,652 lymphocytotoxicity crossmatch reactions performed by 21-37 histocompatibility laboratories were studied in 20 proficiency tests conducted by the South-Eastern Organ Procurement Foundation. Consensus by 75% or more laboratories were obtained on 336 (82.4%) of these test samples: of the 10,410 reactions examined with the use of these consensus cells and sera, only 649 (6.2%) were discordant. Considering positive and negative reactions separately, the discordant (false) positive and negative rates were similar (6.1%, 6.4%, respectively). Varying specific factors in given tests indicated that discordant results were significantly reduced by (1) dispensing sera in trays centrally rather than locally; (2) using a standard one-wash procedure rather than local or three-wash methods; and (3) using reagent (monospecific) rather than patient (polyspecific) sera. Use of standard versus local rabbit complement did not significantly influence the concordance of results.

Cytotoxicity Tests, Immunologic↗

Inhibition of vessel allograft rejection by endothelial removal. Morphologic and ultrastructural changes.

The vascular endothelium plays an important and complex role in vascular allograft rejection. Antigens expressed by the endothelium can act to promote and be the target of rejection reactions, which often lead to thrombosis and ischemic necrosis of the allograft. In this study, segments of femoral artery and femoral vein with or without endothelium were grafted between allogenic or autologous control rats. Immunocompetent Lewis (RT1(1] recipient rats were randomly selected for groups (N = 14 for each) receiving the following: ACI- (RT1a) allografts with intact endothelium, allografts with endothelium removed before operation, autografts with endothelium, and autografts with endothelium removed. Rejection was assessed by graft patency as well as morphologic and ultrastructural changes. At 5 days, the allografts with intact endothelium were totally occluded, whereas allografts without endothelium remained patent, as did autologous control grafts with or without endothelium. Two additional groups (N = 14 each) receiving the de-endothelialized allografts or autografts were examined at 120 days after operation, revealing that grafts in both groups were still patent and had been re-endothelialized. These findings indicate that physical removal of vascular endothelium may depress vessel allograft rejection without immunosuppressive therapy.

Animals↗