Decreased TGF-ß1 and VEGF Release in Cystic Fibrosis Platelets: Further Evidence for Platelet Defects in Cystic Fibrosis.

ABSTRACT

PURPOSE: Cystic fibrosis (CF) patients suffer from chronic lung inflammation. This inflammation may activate platelets. There are limited data on the role of platelet-secreted cytokines in CF. Platelet cytokines with inflammatory effects include vascular endothelial growth factor (VEGF) and transforming growth factor-ß1 (TGF-ß1). As levels of these cytokines are tenfold greater in serum than plasma due to platelet release, serum levels may be one index of platelet content, but a more specific index is release during the aggregation of isolated platelets. We postulated that altered release of these platelet cytokines occurs in CF. METHODS: We obtained sera and plasma from CF outpatients (n = 21) and from healthy controls (n = 20), measured VEGF and TGF-ß1, assessed for correlations with platelet number, analyzed cytokine release during platelet aggregation to collagen, and analyzed differences in maximal platelet aggregation. RESULTS: Platelet number and maximal aggregation levels were higher in CF. Plasma and serum levels of TGF-ß1 and VEGF were higher in CF, but these levels were similar after adjusting for platelet number (serum cytokines correlated with platelet count). The release of VEGF and TGF-ß1 during aggregation was decreased in CF platelets (by 52 and 29 %, respectively). CONCLUSION: Platelet release is not a source of the elevated blood proinflammatory cytokines TGF-ß1 and VEGF in CF, as platelets from CF patients actually release less of these cytokines. These data provide further evidence for platelet defects in CF.