Increased sensitivity to extracellular ATP of fibroblasts from patients affected by systemic sclerosis

Systemic sclerosis (SSc) is an autoimmune disease characterised by an excessive production of collagen and other constituents of the extracellular matrix in the skin, lung and other internal organs, by damage of the microvascular endothelium, and dysregulation of cytokine secretion.1-3 Recent studies show that extracellular nucleotides trigger cytoplasmic Ca2+ increases ([Ca2+]i), morphological changes and cytokine secretion in human fibroblasts.4 Nucleotides are released in response to traumas or inflammation, thus they may also affect fibroblast responses in scleroderma.5 We investigated intracellular second-messenger generation, cytokine secretion and morphological changes in involved, non-atrophic skin biopsies from five patients with the diffuse form of SSc.6 Fibroblasts from patients with SSc had a high rate of spontaneous interleukin (IL)-6 release, which was further enhanced by stimulation with ATP (fig 1A). Changes in intracellular ion homeostasis ([Ca2+]i) and plasma membrane potential occurred at much lower ATP concentrations in fibroblasts from patients . . .