Hyperacute or acute accelerated rejection caused by preformed antibody in sensitized patients resulted in increased waiting period and complicated posttransplant hospital course. Intravenous immunoglobulin (IVIG) has known to have anti cytotoxic effect by blocking the anti HLA antibody. PURPOSE: We investigated the effect of IVIG on hyperacute and acclerated rejection of the heart graft in the presensitized rat. METHODS: Recipients (Wistar) were sensitized from repeated allo (Lewis) skin graft and followed by heterotopic allo cardiac transplantation. A guinea pig was used for the xenotransplantation model. IVIG (Green Cross kappa, 400 mg/kg in allotransplantation, 800 mg/kg in xenotransplantation) was given just before heart transplantation. Graft survival and donor specific IgG, IgM and complement were measured. RESULTS: Graft survival was 7.2 days in non sensitized allogenic heart transplantation (n=9), 1.3 days in sensitized allogenic recipients (n=7). Graft survival was prolonged from 1.3 days to 4.4 days with IVIG treatment (n=5). As for xenogenic transplantation, graft survival was prolonged from 30 min to 7.4 hr with IVIG treatment (n=5). Donor specific IgG and IgM and complement increment were blocked by IVIG during the IVIG treatment. Donor specific IgG and Ig M and complement were increased after the cessation of IVIG treatment. CONCLUSION: IVIG was able to prolong the graft survival of the sensitized allograft and xenograft. Suppression of the donor specific IgG, IgM and complement might be one of the underlying mechanisms. A further studies have to follow to clarify the more detailed mechanism.
Allografts ; Animals ; Complement System Proteins ; Graft Survival ; Guinea Pigs ; Heart Transplantation* ; Heart* ; Heterografts ; Humans ; Immunoglobulin G ; Immunoglobulin M ; Immunoglobulins* ; Immunoglobulins, Intravenous ; Rats* ; Skin ; Tissue Donors ; Transplantation, Heterologous ; Transplants

PURPOSE: Transplantation of pancreas islet has been worldwidely studied as a one of therapeutic modalities to achieve the insulin independence. We studied whether the expression of vascular endothelial growth factor (VEGF) on pancreas islets with liposomal VEGF gene transfer could improve the efficacy of early implantation and long term graft survival in pancreatic islet cell transplantation. METHODS: Syngenic pancreas islets were transplanted beneath the renal capsule. Islets were transfected with plasmid VEGF c-DNA using cationic liposome DMRIE-C. Glucose metabolism and histologic findings were compared between the groups transplanted with VEGF DNA containing islets (n=5) and the control group with (n=5) or without (n=4) local recombinant VEGF adminstration during islet transplant. RESULTS: Glucose was controlled at 5.5 days after transplantation in control group without r-VEGF adminstration, at 4 days in group with recombinant VEGF adminstration, and at 6.6 days in group with VEGF DNA transfected islets. Euglycemia was maintained over 150 days in control group. However, graft failure was developed in 22 days after transplantation in group with VEGF DNA transfected islet. Histologically there were severe infiltrations of neutrophil and lymphocyte in VEGF DNA transfected grafts from 5 days after transplantation. CONCLUSION: Although VEGF could be a favorable angiogenic factor in pancreas islet transplantation, VEGF expression following VEGF DNA transfection into islets could not increase the graft survival due to inflammatory process. More investigations are needed to clarify the mechanism on destructive process of islets after gene transfection into islets, and another approaches to get the effect of gene transfection should be followed.
Angiogenesis Inducing Agents ; Cell Transplantation* ; DNA ; Endothelial Growth Factors* ; Glucose ; Graft Survival* ; Insulin ; Islets of Langerhans Transplantation ; Islets of Langerhans* ; Liposomes ; Lymphocytes ; Metabolism ; Neutrophils ; Pancreas ; Plasmids ; Transfection* ; Transplants* ; Vascular Endothelial Growth Factor A

No abstract available.
Cell Line*

Asthma is characterized by airway inflammation induced by immune dysfunction to inhaled antigens. Although respiratory viral infections are the most common cause of asthma exacerbation, immunologic mechanisms underlying virus-associated asthma exacerbation are controversial. Clinical evidence indicates that nitric oxide (NO) levels in exhaled air are increased in exacerbated asthma patients compared to stable patients. Here, we evaluated the immunologic mechanisms and the role of NO synthases (NOSs) in the development of virus-associated asthma exacerbation. A murine model of virus-associated asthma exacerbation was established using intranasal challenge with ovalbumin (OVA) plus dsRNA for 4 weeks in mice sensitized with OVA plus dsRNA. Lung infiltration of inflammatory cells, especially neutrophils, was increased by repeated challenge with OVA plus dsRNA, as compared to OVA alone. The neutrophilic inflammation enhanced by dsRNA was partly abolished in the absence of IFN-gamma or IL-17 gene expression, whereas unaffected in the absence of IL-13. In terms of the roles of NOSs, dsRNA-enhanced neutrophilic inflammation was significantly decreased in inducible NOS (iNOS)-deficient mice compared to wild type controls; in addition, this phenotype was inhibited by treatment with a non-specific NOS inhibitor (L-NAME) or an specific inhibitor (1400 W), but not with a specific endothelial NOS inhibitor (AP-CAV peptide). Taken together, these findings suggest that iNOS pathway is important in the development of virus-associated exacerbation of neutrophilic inflammation, which is dependent on both Th1 and Th17 cell responses.
Animals ; Asthma/*immunology/virology ; Imines/pharmacology ; Mice ; Mice, Inbred BALB C ; NG-Nitroarginine Methyl Ester/pharmacology ; Nitric Oxide Synthase Type II/antagonists & inhibitors/*metabolism ; RNA, Double-Stranded/metabolism ; Th1 Cells/*immunology ; Th17 Cells/*immunology