A549 cells can express interleukin-16 and stimulate eosinophil chemotaxis

Alveolar epithelial cells produce many types of chemokines such as regulate d on activation, normal T cells expressed and secreted (RANTES), eotaxin in duced by interleukin (IL)-1 beta, or tumor necrosis factor (TNF)-alpha and may contribute to allergic disease by recruiting eosinophils. However, iden tification of the eosinophil chemotacic activity (ECA) release from A549 ce lls, an alveolar type II cell line, has not yet been completed. Recently, I L-16 was also reported to be a potent chemotactic stimulus for CD4(+) T lym phocytes and eosinophils in asthma and other pulmonary diseases. To test th e possibility that alveolar epithelial cells produce IL-16, we analyzed RNA and culture supernatant from A549 cells by reverse transcription/polymeras e chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Th e release of ECA from A549 cells was assessed using a blind-well chemotacti c chamber. IL-16 release was increased in a concentration-dependent manner by stimulation with IL-1 beta or TNF-alpha. A549 cells also expressed IL-16 messenger RNA. The combination of IL-4 and IL-1 beta or TNF-alpha had an a dditive effect on IL-16 production. The release of ECA was induced by IL-1 beta or TNF-alpha in a dose-dependent manner. The combination of these cyto kines had a greater effect than one alone. The blockade of eotaxin and IL-1 6 caused 70% inhibition of ECA, but anti-RANTES antibodies only caused 30% inhibition and anti-IL-8 antibodies failed to affect inhibition. These find ings suggest a role for chemokines released by alveolar epithelial cells in the recruitment of eosinophils into the lung in pulmonary disorders such a s asthma and interstitial lung diseases, and suggested that eotaxin and IL- 16 are potent and effective eosinophil chemoattractants.