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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]

Tests the hypothesis that bleomycin stimulates A549 cells, a type II pneumocyte cell line, to release neutrophil and monocyte chemotactic activities (NCA and MCA). Harvesting of A549 cell supernatant fluids; Partial characterization of the released NCA amd MCA; Performance of checkerboard analysis.

Presents a study which examined the possibility of human lung fibroblasts (HLFs) releasing the mediators which are responsible for monocyte chemokinetic activity (MCA) constitutively. Identification of four peaks of MCA; Inhibition of corresponding molecular-weight peaks separated by molecular-sieve column; Performance of the chemotaxis assay.

Demonstrates that human lung fibroblasts release chemotactic activity for neutrophils and monocytes in response to cyclophosphamide in a dose- and time-dependent manner. Indication that both neutrophil and monocyte activities were chemotactic; Suggestion that lung fibroblasts may modulate inflammatory cell recruitment into the lung by releasing neutrophil and monocyte in response to cyclophosphamide.