RESUMO

Liver interstitial dendritic cells (DC) have been implicated in immune regulation and tolerance induction. We found that the transmembrane immuno-adaptor DNAX-activating protein of 12 kDa (DAP12) negatively regulated conventional liver myeloid (m) DC maturation and their in vivo migratory and T cell allostimulatory ability. Livers were transplanted from C57BL/6(H2(b) ) (B6) WT or DAP12(-/-) mice into WT C3H (H2(k) ) recipients. Donor mDC (H2-K(b+) CD11c(+) ) were quantified in spleens by flow cytometry. Anti-donor T cell reactivity was evaluated by ex vivo carboxyfluorescein diacetate succinimidyl ester-mixed leukocyte reaction and delayed-type hypersensitivity responses, while T effector and regulatory T cells were determined by flow analysis. A threefold to fourfold increase in donor-derived DC was detected in spleens of DAP12(-/-) liver recipients compared with those given WT grafts. Moreover, pro-inflammatory cytokine gene expression in the graft, interferon gamma (IFNγ) production by graft-infiltrating CD8(+) T cells and systemic levels of IFNγ were all elevated significantly in DAP12(-/-) liver recipients. DAP12(-/-) grafts also exhibited reduced incidences of CD4(+) Foxp3(+) cells and enhanced CD8(+) T cell IFNγ secretion in response to donor antigen challenge. Unlike WT grafts, DAP12(-/-) livers failed to induce tolerance and were rejected acutely. Thus, DAP12 expression in liver grafts regulates donor mDC migration to host lymphoid tissue, alloreactive T cell responses and transplant tolerance.

Assuntos

RESUMO

A survey of existing data suggests that trophoblast cells produce factors involved in extracellular matrix degradation. In this study, we correlated the expression of cathepsins D and B in the murine ectoplacental cone with the ultrastructural progress of decidual invasion by trophoblast cells. Both proteases were immunolocalized at implantation sites in lysosome-endosome-like compartments of trophoblast giant cells. Cathepsin D, but not cathepsin B, was also detected ultrastructurally in extracellular compartments surrounded by processes of the invading trophoblast containing extracellular matrix components and endometrial cell debris. The expression of cathepsins D and B by trophoblast cells was confirmed by RT-PCR in ectoplacental cones isolated from implantation chambers at gestation day 7.5. Our data addressed a positive relationship between the expression and presence of cathepsin D at the extracellular compartment of the maternal-fetal interface and the invasiveness of the trophoblast during the postimplantation period, suggesting a participation of invading trophoblast cells in the cathepsin D release. Such findings indicate that mouse trophoblast cells might exhibit a proteolytic ability to partake in the decidual invasion process at the maternal-fetal interface.

Assuntos

Assuntos

RESUMO

OBJECTIVE: We evaluated the efficacy of intravenous gamma-globulin (IVGG) administration for children with Kawasaki disease to establish whether additional, more advanced therapy is needed in intractable cases. STUDY DESIGN: A total of 193 children with Kawasaki disease were studied retrospectively. Patients were admitted 3 to 7 days after the onset of the disease, and IVGG was administered. Laboratory measurements including white blood cell (WBC), neutrophil, and platelet counts and C-reactive protein (CRP) and albumin concentrations were determined before and 2 to 3 days after IVGG treatment. The progression of coronary artery lesions (CALs) was monitored by serial echocardiography until 30 days after treatment. RESULTS: Of 193 children, 24 (12.2 %) had CALs including transient dilatation. In contrast to the other measurements, the WBC count increased in 21 of 24 (87.5%) children with CALs after IVGG therapy. The patients with increased neutrophil count and CRP concentration after IVGG therapy also had CAL formation at a high rate (78.3% and 66.7%, respectively). Among children with normal coronary arteries, elevations of the WBC and neutrophil counts and CRP concentration were observed after IVGG therapy in only 3, 6, and 8 patients, respectively (specificity: 98.2%, 97.0%, and 95.3%, respectively). Furthermore, multiple logistic regression indicated that these variables were useful predictors of CALs in KD. CONCLUSION: Though the introduction of IVGG therapy has improved the prognosis of Kawasaki disease, approximately 10% of patients still develop CALs. The need for more aggressive therapy in IVGG-resistant cases can be recognized early by increases in the WBC and neutrophil counts and serum CRP concentration after IVGG administration.

Assuntos

RESUMO

A male infant with typical clinical and biochemical findings of Zellweger syndrome, but in whom hepatic peroxisomes were detected by electron microscopy, had profound hypotonia, hepatomegaly, typical facial appearance including large fontanelle and frontal bossing, convulsions, panaminoaciduria, and hyperammonemia. He died of liver failure at age 5 months. There were increased levels of very long chain fatty acids and trihydroxycoprostanic acid in serum, and increased excretion of dicarboxylic acids and tyrosine metabolites in the urine. Levels of peroxisomal enzymes, acyl coenzyme A oxidase, bifunctional protein, 3-ketoacyl coenzyme A thiolase, and dihydroxyacetone phosphate acyltransferase in the liver tissue from the patient were all deficient, findings consistent with Zellweger syndrome. However, immunocytochemical study and electron microscopic examination of the liver at autopsy revealed that hepatic peroxisomes were present at a level similar to that in a control subject. These observations suggest further heterogeneity in Zellweger syndrome and a different pathogenesis in this variant case.

Assuntos