Bradykinin stimulates type II alveolar cells to release neutrophil and monocyte chemotactic activity and inflammatory cytokines

In the present study, we evaluated the potential of bradykinin (BK) to indu ce the release of neutrophil and monocyte chemotactic activity (NCA and MCA ) and cytokines from an alveolar type II epithelial cell line, A549 cells. BK stimulated A549 cells to release NCI and MCA in a dose- and time-depende nt manner (P < 0.001), Checkerboard analysis revealed that both NCA and MCA involved chemotactic and chemokinetic activity. Molecular sieve column chr omatography showed three molecular weight masses (near 19 kd, 8 kd, and 400 d) for NCA and several molecular weight peaks (near 66 kd, 25 kd, 19 kd, 1 6 kd, and 400 d) for MCA. The release of NCA and MCA was inhibited by cyclo heximide and lipoxygenase inhibitors (P < 0.01), The NCA and MCA were inhib ited by leukotriene B4 (LTB4) receptor antagonist(P < 0.01), and the concen tration of LTB4 was high enough for NCA and MCA, Antibodies to interleukin (IL)-8 and granulocyte colony-stimulating factor (G-CSF) attenuated NCA (P < 0.01), and antibodies to monocyte chemotactic protein-1 (MCP-1), G-CSF, a nd transforming growth factor (TGF)-beta attenuated MCA (P < 0.01), The lev els of IL-8, G-CSF, MCP-1, and TGF-beta increased time dependently(P < 0.01 ), BK also stimulated the release of ILeukin-6 from A543 cells (P < 0.001). The receptors responsible for the release of NCA, MCA, and individual chem okines involved both BKB1 and BKB2 receptors, These data suggest that BK ma y stimulate alveolar type II pneumocytes to release inflammatory cytokines, which then may modulate the lung inflammation.