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Methotrexate-induced pneumonitis has been reported as an infrequent but potentially serious complication of therapy in a variety of malignant and benign conditions. Because inflammatory cell infiltration is concerned with the development of methotrexate-induced pneumoinitis, and because airway epithelial cells participate in the orchestration of lung inflammation, the authors determined whether methotrexate might stimulate airway epithelial cells (A549 cells) to release neutrophil, monocyte, and eosinophil chemotactic activities (NCA, MCA, and ECA). A549 cells released NCA, MCA, and ECA in a dose- and time-dependent manner in response to methotrexate. Partial characterization revealed the heterogeneity of NCA, MCA, and ECA. The release of chemo-tactic activity was blocked by lipoxygenase inhibitors and cycloheximide. NCA was inhibited by leukotriene (LT) B[SUB4] receptor antagonist, and anti-interleukin (IL)-8 and granulocyte colony-stimulating factor (G-CSF) antibodies. MCA was attenuated by LTB[SUB4] receptor antagonist, and anti-monocyte chemoattractant protein (MCP)-1 and granulocyte-macrophage CSF (GM-CSF) (antibodies. ECA was attenuated by LTB[SUB4] receptor antagonist, and anti-IL-8 and GM-CSF antibodies. The release of IL-8, G-CSF, MCP-1, GM-CSF, and LTB[SUB4] from A549 cells significantly increased in response to methotrexate. The mRNA expression of IL-8 and MCP-1 was augmented by methotrexate stimulation. These data suggest that type II epithelial cells may modulate inflammatory cell recruitment into the lung by releasing NCA, MCA, and ECA in response to methotrexate. [ABSTRACT FROM AUTHOR]

Histamine and serotonin are important inflammatory mediators in the pathophysiology of asthma, and asthmatic patients have higher plasma histamine and serotonin levels than nonasthmatic control subjects. Eotaxin, a potent eosinophil-specific chemotactic factor, is increased in the lower respiratory tract of allergic patients. Recently, lung fibroblasts have been reported to produce eotaxin and are suggested to be the major cellular source of eotaxin. We postulated that lung fibroblasts might release eotaxin in response to histamine or serotonin. To test this hypothesis, we evaluated the potential of histamine or serotonin to induce the release of eotaxin by the human fetal lung fibroblast cell line, HFL-1. HFL-1 released eotaxin in response to histamine and serotonin in a dose- and time-dependent manner (p < 0.05). Histamine or serotonin treatment of HFL-1 augmented the expression of eotaxin mRNA. Eosinophil chemotactic activity by HFL-1 supernatant fluids was inhibited by anti-human eotaxin-neutralizing antibody. These findings lead to the hypothesis that lung-fibroblast-derived eotaxin may in part be responsible for the eosinophil infiltration observed in allergic disease of the airways.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Growing evidence obtained from human genomic analysis and antigen-challenged transgenic mice suggests that interleukin-9 (IL-9) is a candidate factor in immunoglobulin E (IgE) production and thus is thought to be associated with bronchial inflammation and bronchial hyperresponsiveness (BHR). To evaluate the expression of the IL-9 receptor and its effect on the IL-9 human bronchial cell line BEAS-2B cells, reverse transcriptase-polymerase chain reaction (RT-PCR), immunohistochemical investigation, and chemotaxis assay were performed. The components of the IL-9 receptor, consisting of IL-9 receptor α (CD129) and IL-2 receptor γ (CD132), were expressed on BEAS-2B cells as determined by RT-PCR and flow cytometry. BEAS-2B cells exposed to IL-9 released neutrophil chemotactic activity (NCA) in a time- and dose-dependent manner, and the presence of granulocyte colony-stimulating factor (G-CSF) was also detected. This factor is primarily involved in NCA for the measurement of cytokines and in the inhibition assay of neutrophil chemotaxis. These findings suggest that bronchial epithelial cells may express IL-9 receptors, and that IL-9 may induce airway inflammation through the release of G-CSF from bronchial epithelial cells. [ABSTRACT FROM AUTHOR]

Presents information on a study which determined that human lung fibroblasts (HLF) release activity for neutrophils and monocytes in response to cyclophosphamide in a dose- and time-dependent manner. Materials and methods; Results and discussion.

Eotaxin, a potent eosinophil-specific chemotactic factor, is increased in the lower respiratory tract of asthma patients. Recently, lung fibroblasts have been reported to produce eotaxin and their activation can be modulated by inflammatory cytokines. To test the hypothesis that inflammatory cytokines modulate the eotaxin release from lung fibroblasts, we investigated the potential of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), or interferon-γ (IFN-γ) to induce the release of eotaxin and eotaxin mRNA by the human fetal lung fibroblast cell line, HFL-1, was evaluated. HFL-1 released eotaxin constitutively without stimulation, but IL-1β or TNF-α stimulated eotaxin release in a dose- and time-dependent manner. IL-1β or TNF-α treatment of HFL-1 also resulted in the augmented expression of eotaxin mRNA. Although IFN-γ alone had negligible effect on eotaxin release and mRNA expression, IFN-γ induced a significant, concentration-dependent attenuation of eotaxin release and eotaxin mRNA expression from HFL1 stimulated with IL-1β or TNF-α . These findings are consistent with the concept that lung fibroblast-derived eotaxin may in part be responsible for the eosinophil infiltration observed in the airways ofasthmatic patients and that network ofcytokines may modulate the eosinophil recruitment to the airways by stimulation of fibroblasts to release eotaxin. [ABSTRACT FROM AUTHOR]

Focuses on a study which examined the potential for several lipopolysaccharides obtained from Escherichia coli and Pseudomonas aeruginosa to release neutrophil chemotactic activity from lung cells. Materials and methods; Results; Discussion and conclusion.

Provides information on a study which hypothesized that smoke extract might stimulate lung fibroblasts to release neutrophil (NCA) and monocyte (MCA) chemotactic activities. Release of NCA and MCA from human fetal lung (HFL1) fibroblasts; Partial characterization of NCA and MCA; Result of the molecular-sieve column chromatography; Effects of metabolic inhibitors.

Presents information on a study which showed the effects of oxygen and nitrogen metabolites on monocyte chemoattractant protein activity in vitro. Methodology; Results; Discussion of the results.

Focuses on study which postulated that bleomycin might stimulate A549 cells, a type II pneumocyte cell line, to release neutrophil and monocyte chemotactic activities (MCA/NCA). Information on the release of NCA and MCA from A549 cells; Partial characterization of NCA and MCA; Molecular-sieve column chromatographic findings of the released chemotactic activity.

Presents information on a study which investigates whether neurological transmitters including acetylcholine stimulate alveolar macrophages to release neutrophil, monocyte and eosinophil chemotactic activities. Activity of inflammatory cells during injurious processes; Materials and methods of the study; Key findings of the study.

Determines whether A549 cells, a type II pneumocyte cell line, might release mediators responsible for monocyte chemoattractant activity (MCA) constitutively. Release of MCA from A549 cells; Partial characterization of MCA; Effects of leukotriene B4 (LTB4) and platelet activating factor (PAF) receptor antagonists on MCA.

Presents information on a study which evaluates the potential chemotactic activity of alveolar type II-like cells. Methodology; Granulocytic functions of cells; Culture and identification of ATII cells.

Examines whether human lung fibroblasts (HLF) may release mediators that are responsible for monocyte chemokinetic activity (MCA). Review of literature; Methodology of the study; Results.