Eosinophil transendothelial migration induced by the bronchoalveolar lavage fluid of acute eosinophilic pneumonia.

BACKGROUND AND OBJECTIVE: Acute eosinophilic pneumonia (AEP) is characterized by a massive pulmonary infiltration of eosinophils. Mechanisms regulating the selective accumulation of eosinophils in AEP have not been fully established. The objective of this study was to evaluate the mechanisms of eosinophil accumulation in alveolar spaces through examination of bronchoalveolar lavage fluid (BALF) from AEP patients (AEP-BALF). METHODS: Eosinophils were isolated from the blood of healthy subjects and were placed on a human pulmonary microvascular endothelial cell monolayer cultured on Transwell filters (Coster, Cambridge, MA, USA). A saline control solution or BALF from patients with AEP, sarcoidosis or hypersensitivity pneumonitis was applied to the lower compartment, and the transendothelial migration of the eosinophils was evaluated. The concentrations of cytokines and chemokines in BALF were also measured. RESULTS: Transmigration of eosinophils across endothelial cells was only induced by the AEP-BALF. This transmigration was blocked by anti-ß2 integrin mAb. The concentrations of eotaxin-2 and monocyte chemotactic protein (MCP)-4, which are CC chemokine receptor (CCR) 3 ligands, were elevated in the AEP-BALF, and anti-CCR3 mAb or anti-MCP-4 mAb inhibited the AEP-BALF-induced transmigration of eosinophils. Furthermore, the concentration of leukotriene (LT) B4 was increased in the AEP-BALF, and an LTB4 receptor antagonist partially suppressed the AEP-BALF-induced transmigration of eosinophils. CONCLUSION: These findings suggest that CCR3 ligands including eotaxin-2 and MCP-4, and LTB4 play a role in the accumulation of eosinophils in AEP.

Identification of an enhancer that controls up-regulation of fibronectin during differentiation of embryonic stem cells into extraembryonic endoderm.

The extraembryonic endoderm is derived from inner cell mass cells of the blastocyst during early mouse embryogenesis. Formation of the extraembryonic endoderm, which later contributes to the yolk sac, appears to be a prerequisite for subsequent differentiation of the inner cell mass. While embryonic stem cells can be induced to differentiate into extraembryonic endoderm cells in vitro, the molecular mechanisms underlying this process are poorly understood. We used a promoter trap approach to search for genes that are expressed in embryonic stem cells and are highly up-regulated during differentiation to the extraembryonic endoderm fate. We showed that fibronectin fits this expression profile. Moreover we identified an enhancer in the 12th intron of the fibronectin locus that recapitulated the endogenous pattern of fibronectin expression. This enhancer carries Sox protein-binding sequences, and our analysis demonstrated that Sox7 and Sox17, which are highly expressed in the extraembryonic endoderm, were involved in enhancer activity.

[Trends in drug-resistant tuberculosis in National Higashisaitama Hospital, 1994-2001].

To know the prevalence of resistance to four first-line anti-tuberculosis drugs, we reviewed the results of drug-susceptibility tests of patients with tuberculosis who were admitted to our hospital from 1994 to 2001. Among patients with no prior chemotherapy against tuberculosis, the complete resistance rate was 1.9% for INH, 0.81% for RFP, 5.1% for SM, 0.81% for EB, and 0.32% for multiple drug-resistance (MDR). The acquired resistance rate was 9.7% for INH, 11.5% for RFP, 7.3% for SM, 2.4% for EB, and 6.1% for MDR. There was no significant increase in the prevalence of drug resistance between the first half (1994-1997) and the latter half (1998-2001) of the investigation periods. Compared with the previous reports, our results indicated no increase in the prevalence of drug resistance in tuberculosis patients with no prior treatment and the decrease of prevalence in patients with prior treatment of tuberculosis. A multi-drug regimen consisted of INH, RFP, PZA and EB or SM, which is currently considered as a standard regimen of tuberculosis chemotherapy and used quite widely, does not seem to induce the increase of drug-resistant tuberculosis.