Tang Liping, Jiang Weiwu, Welty Stephen E
Biomedical Engineering Program, University of Texas at Arlington, PO Box 19138, Arlington, TX 76019-0138, USA.
J Biomed Mater Res. 2002 Dec 15;62(4):471-7. doi: 10.1002/jbm.10271.
Biomaterial-mediated inflammatory responses often compromise the functions of implantable devices. The mechanism(s) involved in the inflammatory responses, which can be arbitrarily divided into phagocyte transmigration, chemotaxis, and adhesion to implant surfaces, are not totally understood. Because adhesion molecules have been shown to involved in phagocyte transmigration, this study was designed to investigate the participation of endothelial adhesion molecules in the pathogenesis of biomaterial-mediated inflammatory responses and fibrotic tissue formation. Using transgenic adhesion molecule knockout mice, we found that (1) deficiency of P-selectin reduced polymorphonuclear neutrophils (PMN) but not macrophages/monocytes (Mphi) transmigration and adhesion. (2) Furthermore, absence of both P- and E-selectin (P/E-deficient) dramatically diminished both PMN and Mphi recruitment to the peritoneal cavity and accumulation on implanted biomaterials. (3) Finally, the impairment of inflammatory responses in P/E-deficient mice significantly reduced the extent of subsequent biomaterial-mediated fibrotic responses. We conclude that P- and E-selectins are important for both biomaterial-mediated inflammatory and fibrotic reactions. Our results also indicate that the reduction of phagocyte accumulation might be responsible to the decrease of fibrotic tissue formation surrounding material implants. Better understanding of such sequence of events may help the rational design of biomaterials with desired tissue reactivity.
生物材料介导的炎症反应常常会损害可植入装置的功能。炎症反应所涉及的机制（可任意分为吞噬细胞迁移、趋化作用以及对植入物表面的黏附）尚未完全明确。由于已表明黏附分子参与吞噬细胞迁移，本研究旨在探究内皮黏附分子在生物材料介导的炎症反应和纤维化组织形成发病机制中的作用。利用转基因黏附分子敲除小鼠，我们发现：（1）P-选择素缺乏会减少多形核中性粒细胞（PMN）的迁移和黏附，但不会减少巨噬细胞/单核细胞（Mphi）的迁移和黏附。（2）此外，P-选择素和E-选择素均缺失（P/E双缺失）会显著减少PMN和Mphi向腹腔的募集以及在植入生物材料上的聚集。（3）最后，P/E双缺失小鼠炎症反应的受损显著降低了随后生物材料介导的纤维化反应的程度。我们得出结论，P-选择素和E-选择素对生物材料介导的炎症和纤维化反应均很重要。我们的结果还表明，吞噬细胞积累的减少可能是材料植入周围纤维化组织形成减少的原因。更好地理解此类事件序列可能有助于合理设计具有所需组织反应性的生物材料。
