Larsen Kristoffer, Macleod David, Nihlberg Kristian, Gürcan Eylem, Bjermer Leif, Marko-Varga György, Westergren-Thorsson Gunilla
Experimental Medical Science, Lund University, BMC C13, S-221 84 Lund, Sweden.
J Proteome Res. 2006 Jun;5(6):1479-83. doi: 10.1021/pr050462h.
Haptoglobin is an acute-phase glycoprotein considered to be involved in tissue repair and is produced by fibroblasts and inflammatory cells. By using a gel-based proteomic approach, we show for the first time a possible role for haptoglobin in the differentiation of fibroblast progenitor cells, termed fibrocytes, in patients with mild asthma. Bronchoalveolar lavage fluid (BALF) was performed to sample circulating fibrocytes from patients with mild asthma and nonasthmatic control subjects. Fibrocytes from the airway lumen were characterized by triple staining of the markers CD34/CD45R0/alpha-smooth muscle actin, and subjected to confocal microscopy. The protein expression pattern was analyzed using two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF). Elevated levels of haptoglobin expression in BALF was reported in a sub-group of patients with mild asthma (p < 0.05) when compared to the other subjects. In addition, this increase in haptoglobin was accompanied by differentiation of fibrocytes into fibroblast-like cells. When further analyzing the expression pattern of haptoglobin isoforms, a heterozygous expression was detected in the patients where fibrocyte differentiation could be observed. These data raise the possibility that an acute and specific inflammatory state facilitates the differentiation of fibroblast progenitor cells into activated fibroblasts. Furthermore, this study proposes a novel role for haptoglobin in airway remodeling in patients with asthma.
触珠蛋白是一种急性期糖蛋白，被认为参与组织修复，由成纤维细胞和炎症细胞产生。通过基于凝胶的蛋白质组学方法，我们首次展示了触珠蛋白在轻度哮喘患者中对成纤维细胞祖细胞（即纤维细胞）分化可能发挥的作用。对轻度哮喘患者和非哮喘对照受试者进行支气管肺泡灌洗（BALF）以采集循环中的纤维细胞。通过对标记物CD34/CD45R0/α平滑肌肌动蛋白进行三重染色来鉴定气道腔中的纤维细胞，并进行共聚焦显微镜检查。使用二维电泳（2-DE）和基质辅助激光解吸电离飞行时间（MALDI-TOF）分析蛋白质表达模式。与其他受试者相比，轻度哮喘患者亚组的BALF中触珠蛋白表达水平升高（p < 0.05）。此外，触珠蛋白的这种增加伴随着纤维细胞向成纤维细胞样细胞的分化。在可观察到纤维细胞分化的患者中进一步分析触珠蛋白异构体的表达模式时，检测到杂合表达。这些数据增加了一种可能性，即急性和特异性炎症状态促进成纤维细胞祖细胞分化为活化的成纤维细胞。此外，本研究提出了触珠蛋白在哮喘患者气道重塑中的新作用。
