Shiratori Beata, Zhao Jingge, Okumura Masao, Chagan-Yasutan Haorile, Yanai Hideki, Mizuno Kazue, Yoshiyama Takashi, Idei Tadashi, Ashino Yugo, Nakajima Chie, Suzuki Yasuhiko, Hattori Toshio
Division of Disaster-Related Infectious Diseases, International Research Institute of Disaster Science, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan.
Department of Respiratory Medicine, Fukujuji Hospital, Japan Anti-Tuberculosis Association, 3-1-24 Matsuyama, Kiyose, Tokyo 204-8533, Japan.
Int J Mol Sci. 2016 Dec 22;18(1):19. doi: 10.3390/ijms18010019.
Elevated matricellular proteins (MCPs), including osteopontin (OPN) and galectin-9 (Gal-9), were observed in the plasma of patients with Manila-type tuberculosis (TB) previously. Here, we quantified plasma OPN, Gal-9, and soluble CD44 (sCD44) by enzyme-linked immunosorbent assay (ELISA), and another 29 cytokines by Luminex assay in 36 patients with pulmonary TB, six subjects with latent tuberculosis (LTBI), and 19 healthy controls (HCs) from Japan for a better understanding of the roles of MCPs in TB. All TB subjects showed positive results of enzyme-linked immunospot assays (ELISPOTs). Spoligotyping showed that 20 out of 36 (MTB) strains belong to the Beijing type. The levels of OPN, Gal-9, and sCD44 were higher in TB (positivity of 61.1%, 66.7%, and 63.9%, respectively) than in the HCs. Positive correlations between OPN and Gal-9, between OPN and sCD44, and negative correlation between OPN and ESAT-6-ELISPOT response, between chest X-ray severity score of cavitary TB and ESAT-6-ELISPOT response were observed. Instead of OPN, Gal-9, and sCD44, cytokines G-CSF, GM-CSF, IFN-α, IFN-γ, IL-12p70, and IL-1RA levels were higher in Beijing MTB-infected patients. These findings suggest immunoregulatory, rather than inflammatory, effect of MCPs and can advance the understanding of the roles of MCPs in the context of TB pathology.
此前在马尼拉型肺结核（TB）患者的血浆中观察到包括骨桥蛋白（OPN）和半乳糖凝集素-9（Gal-9）在内的基质细胞蛋白（MCPs）水平升高。在此，我们通过酶联免疫吸附测定（ELISA）对36例肺结核患者、6例潜伏性结核感染（LTBI）受试者和19名来自日本的健康对照（HCs）的血浆OPN、Gal-9和可溶性CD44（sCD44）进行了定量，并通过Luminex测定法对另外29种细胞因子进行了定量，以便更好地了解MCPs在结核病中的作用。所有结核病受试者的酶联免疫斑点测定（ELISPOT）结果均为阳性。寡核苷酸分型显示，36株结核分枝杆菌（MTB）菌株中有20株属于北京型。结核病患者中OPN、Gal-9和sCD44的水平高于健康对照（阳性率分别为61.1%、66.7%和63.9%）。观察到OPN与Gal-9之间、OPN与sCD44之间呈正相关，OPN与ESAT-6-ELISPOT反应之间、空洞型肺结核的胸部X线严重程度评分与ESAT-6-ELISPOT反应之间呈负相关。在北京型MTB感染患者中，细胞因子G-CSF、GM-CSF、IFN-α、IFN-γ、IL-12p70和IL-1RA的水平高于OPN、Gal-9和sCD44。这些发现表明MCPs具有免疫调节而非炎症作用，并有助于推进对MCPs在结核病病理学背景下作用的理解。
