Monocyte chemotactic factors released from type II pneumocyte- like cells in response to TNF-a and IL-1a

Monocyte chemotactic factors released from type II pneumocyte-like cells in response to TNF-a and IL-1a. S. Koyama, E. Sato, H. Nomura, K. Kubo, M. Miura, T. Yamashita, S. Nagai, T. Izumi. #ERS Journals Ltd 1999. ABSTRACT: It has been reported that tumour necrosis factor (TNF)-a and interleukin (IL)-1 induce the release of monocyte chemotactic factors (MCF), including chemokines, from A549 cells, an alveolar type II cell line. However, the relative contribution of these chemokines to MCF is still uncertain. In the present study, the relative contribution of various chemokines released from A549 cells acting as MCF upon stimulation by TNF-a and IL-1a, was evaluated. TNF-a and IL-1a induced the release of MCF in a doseand time-dependent manner (p<0.001). The release of MCF was inhibited by cycloheximide and lipoxygenase inhibitors. Molecular sieve column chromatography revealed multiple peaks of MCF (near 60 kDa, 25±22 kDa, 15±13 kDa, 8 kDa, and 400 Da). Leukotriene B4 (LTB4) receptor-antagonists inhibited MCF by 50% after 24 h and 30% after 72 h. Monocyte chemoattractant protein-1 (MCP-1), transforming growth factor (TGF)-b, "regulated on activation, normal T-cells, expressed and secreted" (RANTES), and granulocyte-macrophage colonystimulating factor (GM-CSF) were released significantly in response to IL-1a and TNF-a, and antibodies to MCP-1, GM-CSF, and RANTES inhibited MCF activity by 40, 5 and 20% after 24 h, and by 50, 20, and 10% after 72 h, respectively. Each antibody or LTB4 receptor-antagonist inhibited the corresponding column chromatography-separated molecular weight peak of MCF. These data suggest that A549 cells release monocyte chemoattractant protein-1 as the predominant monocyte chemotactic factor rather than granulocyte-macrophage colony-stimulating factor, RANTES, and transforming growth factor-b, and that leukotriene B4 is constitutively released as a monocyte chemotactic factor. Eur Respir J 1999; 13: 820±828. *The First Dept of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan. Mitsubishi Kagaku BCL, Itabashiku, Tokyo, Japan. Chest Disease Research Institute, Kyoto University, 53 Shogoinn, Sakyoku, Kyoto, Japan.