Macrolide antibiotics induce apoptosis of human peripheral lymphocytes in vitro.

We previously reported that long-term administration of macrolides (MCL) reduced the number of lymphocytes in bronchoalveolar lavage fluid (BALF) of patients with chronic lower respiratory tract disease. To investigate the anti-inflammatory activity of macrolides, we evaluated their effect on apoptosis of lymphocytes isolated from human peripheral blood. Lymphocytes treated with clarithromycin, azithromycin and josamycin at a final concentration of 200 microg/ml showed positive staining for Annexin V, Fas and Fas ligand using flow cytometry with time at 12-72 h, while other antibiotics did not.

Increased expression of collagen-binding heat shock protein 47 in murine bleomycin-induced pneumopathy.

The 47-kDa heat shock protein 47 (HSP47) is a collagen-specific molecular chaperone that has been shown to play a major role during the processing and/or secretion of procollagen. Expression of HSP47 has been reported to increase in parallel with expression of collagens during the progression of various fibrosis models. The aim of the present study was to investigate the association between HSP47 expression and collagen accumulation in bleomycin (BLM)-induced murine fibrosis.

High concentrations of soluble Fas ligand in bronchoalveolar lavage fluid of patients with pulmonary sarcoidosis.

Background And Objectives: Sarcoidosis is a systematic granulomatous disorder of unknown origin characterized by accumulation of T lymphocytes and macrophages in multiple organs. We postulated that apoptosis through the Fas/Fas ligand (L) system may be associated with regulation of immune reactions characterized by the formation of noncaseous necrotizing granulomas. Soluble (s) FasL is not equivalent to membrane-associated FasL since conversion of membrane-bound FasL to the soluble form is associated with downregulation of cytotoxicity.

Intrapulmonary pharmacokinetics of telithromycin, a new ketolide, in healthy Japanese volunteers.

The concentrations of telithromycin, a new ketolide antimicrobial agent, in alveolar macrophages (AMs) and bronchoalveolar epithelial lining fluid (ELF) were determined in order to investigate the transfer of the drug into target tissue, relative to plasma, following multiple oral doses of telithromycin. Twenty-four healthy male Japanese volunteers were randomly allocated to four groups. Each subject was given 600 or 800 mg of telithromycin once daily for 5 days, followed by bronchoalveolar lavage (BAL) 2 or 8 h after the last dose (group A and B: 600 mg, 2 and 8 h BAL time point; group C and D: 800 mg, 2 and 8 h BAL time point).