Expression of the chemokine RANTES in pulmonary Wegener's granulomatosis

Wegener's granulomatosis (WG) is an inflammatory, destructive, angiotropic lesion. The inflammatory process involves accumulation of macrophages, lymp hocytes, and polymorphonuclear neutrophils. We studied 6 lung biopsy specim ens from patients with WG to characterize the cellular infiltrate and to an alyze the mechanism of immune cell recruitment. We show that lymphocytes ac cumulating in WG lesions are mostly memory CD4(+)CD45RO(+) T lymphocytes an d, although less numerous, CD8(+)CD45RO(+) T lymphocytes. Few if any B lymp hocytes or natural killer cells are present within lesions. The chemokine R ANTES (regulated upon activation in normal T cells, expressed and secreted) has been reported to recruit memory T lymphocytes and macrophages selectiv ely. We used reverse-transcription polymerase chain reaction, in situ hybri dization, and immunohistochemistry to study its production in WG. RANTES wa s expressed at a higher Level in WG lungs than in normal controls, especial ly around microabscesses. As visualized immunohistochemistry in serial sect ions with anti-RANTES monoclonal antibody, RANTES production was produced m ainly by macrophages. Expression of the gene coding for interferon-gamma (I FN-gamma), a potent RANTES inducer, was also studied. Its expression was al so much stronger in WG than in controls. Our observations are consistent wi th a cascade of events leading to the recruitment of immune cells in WG, se quentially involving production of IFN-gamma by T lymphocytes and RANTES pr oduction by macrophages, leading to the homing of memory T-helper lymphocyt es and macrophages. HUM PATHOL 32:320-326. Copyright (C) 2001 by W.B. Saund ers Company.