Cell-free supernatants of sarcoid alveolar macrophages suppress proliferation of sarcoid alveolar fibroblasts

We have reported that alveolar macrophages (AM) isolated from sarcoidosis (SA) patients, as well as cell-free supernatants of these macrophages, markedly suppressed mitogenic stimulation of peripheral blood lymphocyte (PBL). We now show that cell-free supernatants of AM originating from sarcoidosis patients also suppress [³H]thymidine incorporation by fibroblast (Fb) cultures resulting from bronchoalveolar lavages (BAL) of SA: 40.6% inhibition compared with only 8.2% by supernatants of AM obtained from nonsarcoid controls. The clones of proliferating Fb appeared in cultures of BAL cells after most of the macrophages were detached from the tissue culture surface and actively synthesized collagen, as demonstrated by ultrastrural studies. In confirmation with previously reported results, the same supernatants from AM of SA patients also suppressed mitogenic stimulation of PBL (35.7% inhibition of [³H]thymidine incorporation compared with only 16.3% inhibition by control supernatants). They also contained high amounts of IL-1 (178 compared to 9.2 U/ml of control supernatants), whereas the PGE₂ content was within normal levels (0.28 compared to 0.19 ng/ml/10⁵ cells in control supernatants). It is concluded that AM from SA patients release a factor(s) which suppresses the proliferation of alveolar fibroblasts.