ABSTRACT
BACKGROUND AND OBJECTIVE: Bronchiolitis obliterans (BO) has been reported to develop following ingestion of Sauropus androgynus (SA), a leafy shrub distributed in Southeast Asia. Little is known about direct effects of SA on airway resident cells or haematopoietic cells in vitro. Identification of the SA component responsible for the development of BO would be an important key to elucidate its mechanism. We sought to elucidate the direct effects of SA on airway resident cells or haematopoietic cells and identify the SA element responsible for the pathogenesis of BO. METHODS: SA dry powder was partitioned into fractions by solvent extraction. Human and murine monocytic cells, epithelial cells and endothelial cells were cultured with SA solution or fractions eluted from SA. We also investigated the effect of SA in vivo using a murine BO syndrome (BOS) model. RESULTS: The aqueous fraction of SA induced significant increases of inflammatory cytokine and chemokine production from monocytic lineage cells. This fraction also induced significant apoptosis of endothelial cells and enhanced intraluminal obstructive fibrosis in allogeneic trachea allograft in the murine BOS model. We found individual differences in tumour necrosis factor α (TNF-α) production from monocytes of healthy controls stimulated by this aqueous fraction of SA, whereas it induced high-level TNF-α production from monocytes of patients with SA-induced BO. CONCLUSIONS: These results suggest that an aqueous fraction of SA may be responsible for the pathogenesis of BO.
Subject(s)
Bronchiolitis Obliterans/chemically induced , Bronchiolitis Obliterans/pathology , Macrophages, Alveolar/pathology , Malpighiaceae , Plant Extracts/adverse effects , Animals , Apoptosis/drug effects , Bronchiolitis Obliterans/metabolism , Cell Line , Cell Proliferation/drug effects , Cells, Cultured , Disease Models, Animal , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Endothelial Cells/pathology , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Epithelial Cells/pathology , Female , Humans , In Vitro Techniques , Macrophages, Alveolar/drug effects , Macrophages, Alveolar/metabolism , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Monocytes/drug effects , Monocytes/metabolism , Monocytes/pathology , Plant Extracts/pharmacology , Pulmonary Alveoli/drug effects , Pulmonary Alveoli/metabolism , Pulmonary Alveoli/pathology , Tumor Necrosis Factor-alpha/metabolismABSTRACT
BACKGROUND: T-helper (Th)-2 background in the lungs may favor the development of pulmonary fibrosis. We hypothesized that usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP), major pathologic patterns of chronic interstitial pneumonia, would have different expression profiles of TH1 and TH2 chemokines. METHODS: Total RNA was isolated from lung tissues obtained by surgical biopsy (18 cases of UIP and 29 cases of NSIP). The expression of ligands for CXCR3 [TH1 cells chemoattractant: monokine induced by interferon (IFN)-gamma (MIG), IFN-gamma-inducible protein of 10 kD, and IFN-inducible T cell alpha chemoattractant] and ligands for CCR4 [TH2 cells chemoattractant: thymus- and activation-regulated chemokine and macrophage-derived chemokine (MDC)] were analyzed by real-time reverse transcriptase polymerase chain reaction. RESULTS: MIG and IFNgamma-inducible protein of 10 kD expression were significantly higher in NSIP compared with UIP. MDC expression was increased in UIP compared with NSIP, although the difference was not significant. MIG/MDC is significantly elevated in NSIP but not UIP. Interestingly, MIG/MDC was significantly higher in NSIP group 3 (NSIP with extensive fibrosis) compared with UIP. CONCLUSIONS: These results may indicate that these 2 diseases have a different pathophysiology. MIG/MDC may be a useful marker to distinguish these 2 diseases.
Subject(s)
Chemokines/biosynthesis , Gene Expression Regulation/immunology , Lung Diseases, Interstitial/metabolism , Th1 Cells/metabolism , Th2 Cells/metabolism , Aged , Chemokines/genetics , Female , Humans , Lung Diseases, Interstitial/classification , Lung Diseases, Interstitial/immunology , Male , Middle Aged , RNA, Messenger/biosynthesis , Th1 Cells/immunology , Th2 Cells/immunologyABSTRACT
We report the case of a woman with gefitinib-sensitive lung adenocarcinoma, who was successfully re-treated with gefitinib for carcinomatous meningitis as the disease recurrence. The good response to gefitinib treatment was supported in part by the existence of epidermal growth factor receptor mutation in carcinoma cells in the specimen obtained from transbronchial lung biopsy, in which E709G in exon 18 and L858R in exon 21 were shown. Although carcinomatous meningitis had been well controlled by the treatment with gefitinib, serum carcinoembryonic antigen (CEA) level increased with re-growth of primary tumor and development of lymphangitic carcinomatosis. Immunohistochemical findings revealed de novo emergence of CEA-producing carcinoma cells in the biopsy specimen taken after recurrence of pulmonary lesion during re-treatment of gefitinib, but revealed little or no CEA expression in the specimen obtained at first presentation. These facts may suggest the possibility of oligo clonality of carcinoma cells in this case.
Subject(s)
Antineoplastic Agents/pharmacology , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Quinazolines/pharmacology , Adenocarcinoma/drug therapy , Adenocarcinoma/pathology , Aged , Biopsy , Carcinoembryonic Antigen/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , ErbB Receptors/genetics , Exons , Female , Gefitinib , Humans , Lung Neoplasms/pathology , Magnetic Resonance Imaging/methods , Mutation , RecurrenceABSTRACT
In a man aged 34 who had been experiencing frequent coughing since November 2001, a chest radiograph showed infiltration shadows in both lung fields. Chest CT showed diffuse centrilobular nodules and multiple mediastinal lymphadenopathy. Laboratory examination revealed high values for C-reactive protein and the erythrocyte sedimentation rate, together with polyclonal hyperimmunoglobulinemia and an elevated interleukin-6 level. We suspected multicentric Castleman's disease, and so performed thoracoscopic mediastinal lymph node biopsy and lung biopsy. The former disclosed follicular hyperplasia and plasma cell infiltration in the interfollicular area, suggesting a diagnosis of Castleman's disease, plasma cell type. The lung biopsy showed heavy infiltration of plasma cells. The diagnosis was therefore multicentric Castleman's disease (MCD) with pulmonary involvement. The chest CT findings were tpical characteristics of pulmonary involvement in patients with MCD.
