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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]

Investigates whether smoke extract stimulates lung fibroblasts to release neutrophil and monocyte chemotactic activities. Time-related release of neutrophil and monocyte chemotactic activities in response to smoke extract; Partial characterization of released neutrophil and monocyte chemotactic activities; Trypsin sensitivity of the chemotactic activity.

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.

We reviewed the biological functions of CD4+ eosinophils, which are observed in peripheral blood, sputum and bronchoalveolar lavage fluid of various diseases. We have shown that CD4 molecules on human eosinophils are induced by tumor necrosis factor-alpha (TNF-α) stimulation. Interleukin-16 (IL-16) has been reported to bind a natural soluble ligand for the CD4 molecule. We reported that TNF-α-stimulated eosinophils migrate in a time- and dose-dependent manner against IL-16. Theophylline and dexamethasone significantly inhibited CD4 expression. Theophylline inhibited CD4+ eosinophil chemotaxis, but dexamethasone did not. Theophylline may prevent airway inflammation by downregulating the expression of CD4 molecule and CD4+ eosinophil migration. However, dexamethasone may inhibit airway inflammation through the downregulation of CD4 expression.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]