The role of mast cells in fibrosis and pulmonary arterial hypertension in systemic sclerosis

Sonosuke Yukawa1), Kunihiro Yamaoka1), Norifumi Sawamukai1), Shohei Shimajiri2), Kazuyoshi Saito1), Yasuyuki Sasaguri2), Yoshiya Tanaka1)
1)The First Department of Internal Medicine, School of Medicine 2) The Department of Second Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, Japan

Systemic sclerosis (SSc) is characterized by tissue fibrosis and obliterative microangiopathy with increased number of dermis mast cells (MSc). However, the role of MCs in the pathological processes remains unclear. To clarify the role of MCs in human SSc, we have estimated histological features in skin biopsy specimens obtained from SSc patients, non-SSc patients and normal control. Detection of MCs was performed by toluidine blue staining, evaluated with density of MCs (/㎟) in each specimen that was measured by NanoZoomer Digital Pathology. Significantly increased density of MCs with degranulation was observed in dermis of SSc patients in concert with fibrosis. Accordingly, density correlated with modified Rodnan’s skin thickness score, suggesting the relevance of MCs to the progression of sclerosis. It is noteworthy that dermis MCs were increased in cases complicated with pulmonary artery hypertension (PAH). showing strong relation with the mean pulmonary arterial pressure. Furthermore, the density of MCs in pulmonary interstitium in lung biopsy specimen obtained from a case with SSc-related PAH markedlyincreased, co-localizing with pulmonary artery. Furthermore, production of TGF-β1 and PDGF, which are known to be involved in fibrosis, were highly detected in MCs at both dermis and pulmonary interstitum. In conclusion, we here document the role of MCc in the pathological processes of cutaneous fibrosis and PAG in patients with SSc.