The participation of P- and E-selectins on biomaterial-mediated tissue responses.
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.
Tang
Liping
L
Biomedical Engineering Program, University of Texas at Arlington, PO Box 19138, Arlington, TX 76019-0138, USA. ltang@uta.edu
Jiang
Weiwu
W
Welty
Stephen E
SE
D000818:Animals; D001672:Biocompatible Materials; D019040:E-Selectin / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D005355:Fibrosis / Q000378:metabolism; D005549:Foreign-Body Reaction; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D019007:P-Selectin / Q000235:genetics / Q000378:metabolism*; D010586:Phagocytes / Q000378:metabolism*; D019736:Prostheses and Implants
D001672:Biocompatible Materials; D019040:E-Selectin; D019007:P-Selectin; D005340:Fibrinogen