THE SOURCE AND ROLE OF RANTES IN INTERSTITIAL LUNG-DISEASE

The chemokine ''regulated on activation, normal T-cell expressed and s ecreted'' (RANTES) is a potent eosinophil and lymphocyte attractant wi th particular preference for CD45RO+ T-cells and eosinophils, These ce lls accumulate in the lungs of patients with sarcoidosis and fibrosing alveolitis, The purpose of this study was to determine whether RANTES mediates the inflammatory cell influx in these diffuse lung diseases. Cell types and number of bronchoalveolar cells expressing RANTES prot ein were investigated by immunocytochemistry using lavage cells obtain ed from 22 patients and 11 control subjects, Subsequently, RANTES mess enger ribonucleic acid (mRNA) was semiquantitated using reverse transc ription polymerase chain reaction (RT-PCR) methodology in unseparated lavage cell pellets in 26 patients and 13 control subjects, Cells expr essing RANTES mRNA were identified by in situ hybridization. RANTES pr otein expression in lower respiratory tract (LRT) cells was identified in all study groups, The percentage of RANTES+ lavage cells in sarcoi dosis was higher than in controls, RANTES was localized in the cytopla sm, mainly in alveolar macrophages (CD68+ cells) in sarcoidosis, and b oth in alveolar macrophages and eosinophils in fibrosing alveolitis, T he same cell types which expressed RANTES protein expressed RANTES mRN A, as assessed by in situ hybridization. Sarcoidosis patients had high er levels of RANTES mRNA than the other groups, RANTES protein was hig her in individuals with abnormal lymphocyte numbers: RANTES protein an d mRNA expression was significantly correlated with lavage CD45RO+ lym phocyte numbers. These results indicate that RANTES may mediate T-lymp hocyte influx in diffuse lung disease, particularly sarcoidosis, Moreo ver, they suggest that the cellular source of RANTES is the alveolar m acrophage in sarcoidosis, and both macrophages and eosinophils in fibr osing alveolitis.