MODULATION OF FIBROBLAST ACTIVITY IN HISTIOCYTOSIS-X BY PLATELET-DERIVED GROWTH-FACTOR

Platelet-derived growth factor (PDGF) was shown to modulate fibroblast activity in interstitial lung diseases like idiopathic pulmonary fibr osis (IPF). The role of PDGF in fibrosing mechanisms in histiocytosis X is unclear. Eight patients with histiocytosis X, five patients with idiopathic pulmonary fibrosis (IPF), and nine patients with no evidenc e of interstitial lung disease underwent bronchoalveolar lavage (BAL). The c-sis gene (a proto-oncogen encoding for the B-chain of PDGF) exp ression was measured by gene hybridization revealing an upregulated c- sis transcript in the group of histiocytosis X and patients, whereas n o c-sis expression was detectable in the control group. The alveolar m acrophage supernatants from histiocytosis X patients and from the cont rol group were incubated with a human lung fibroblast cell line (WI-38 ). The mitosis rate was measured by tritiated thymidine incorporation and collagen production was estimated by determining the procollagen I II peptide concentration in fibroblast supernatants. Tritiated thymidi ne uptake was increased 1.6 times in histiocytosis X compared with the control group (p<0.01). Procollagen-III-peptide levels in fibroblast supernatants after incubation with alveolar macrophage supernatants fr om histiocytosis X were elevated 2.5 times compared with the control g roup (p<0.01). Prior to incubation with the WI-38 cell line, the cell supernatant then was preincubated with nonpreserved anti-human PDGF (A A- and BB-chain) resulting in an 80% decrease of tritiated thymidine u ptake and procollagen-III-peptide production in the group of histiocyt osis X patients compared with native supernatants. No significant chan ge in fibroblast activity was seen in the control group. Preincubation with nonpreservated Ki-T2 antibodies as pan T-lymphocyte marker did n ot show significant differences in both groups excluding unspecific an tibody inhibition. These findings suggest increased PDGF production by alveolar macrophages in histiocytosis X patients. The PDGF is in part responsible for increased fibroblast replication and collagen product ion.