Angiogenesis in P- and E- Selectin- Deficient Mice D.W. HARTWELL,* C.E. BUTTERFIELD, † P.S. FRENETTE,* ,§ B.M. KENYON, † R.O. HYNES, ‡ J. FOLKMAN, † AND DENISA D. W AGNER* *Center for Blood Research and Departments of Pathology and § Medicine, Harvard Medical School, Boston, MA; † Children’s Hospital and Department of Surgery, Harvard Medical School, Boston, MA; ‡ Howard Hughes Medical Institute, Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA ABSTRACT Objectives: Several observations reported earlier indicated that the selectins, in particular E-selectin, might be involved in angiogenesis; however, mice deficient in the endothelial selectins develop normally. To clarify the role of endothelial selectins in angiogenesis, we have studied experimentally induced angiogenesis in selectin-deficient mice. Methods: Hydron pellets containing either basic fibroblast growth factor or the inflammatory cytokine tumor necrosis factor  were implanted into the corneas of wild-type and P- and/ or E-selectin-deficient mice. Results: The lengths and circumferential range of the newly formed blood ves- sels in the corneas of the endothelial selectin-deficient mice were similar to those of wild-type mice. Conclusion: The endothelial selectins are not essential in experimentally in- duced angiogenesis in vivo. KEY WORDS: angiogenesis, selectins, bFGF, TNF INTRODUCTION Angiogenesis, the generation of new blood vessels by capillary sprouting from established vessels, is a key element in many physiological and pathological pro- cesses such as reproduction, wound healing, and the growth of solid tumors (6,11). This complex process involves production of proteases, migration and pro- liferation of endothelial cells, formation of lumen, and remodeling of extracellular matrix (5). A variety of mediators such as acidic and basic fibroblast growth factors (bFGF), vascular endothelial cell growth factor (VEGF), and tumor necrosis factor  (TNF) have been shown to induce angiogenic re- sponses, although less is known about the molecular or signaling pathways involved. At the cellular level, angiogenesis is characterized by the invasion, migration, and proliferation of endo- thelial cells. Multiple adhesion events, including cell–cell and cell–matrix interactions seem to be es- sential for angiogenesis. Studies have shown that vascular endothelial cells grow in an anchorage- dependent manner, and that blocking integrin  v  3 - mediated signals inhibits angiogenesis by promoting apoptosis of proliferation vascular cells (1,8). In ad- dition, mice deficient in fibronectin, an extracellular matrix molecular, or integrins  5 or  v exhibit pro- found defects in angiogenesis (9,23). Adhesion mol- ecules may affect angiogenesis on multiple levels. In addition to endothelial cell adhesion and migration, they may also influence angiogenesis by facilitating the entry of leukocytes into tissues, which may, in turn, provide angiogenic stimulators or inhibitors. Consistent with this possibility are the findings that Supported by the National Institutes of Health Grants No. HL- 53756 to D.D.W. and P01-CA 45548 to J.F. D.W.H. was sup- ported by Individual National Service Award HL-09264 and P.S.F. by a fellowship from the Medical Research Council of Canada. For reprints of this article, contact: Denisa D. Wagner, PhD, Center for Blood Research, Harvard Medical School, 800 Hun- tington Avenue, Boston, MA 02115, USA. Received 9 May 1997; accepted 1 December 1997 Microcirculation (1998) 5, 173–178 © 1998 Stockton Press All rights reserved 1073-9688/98 $12.00 http:/ / www.stockton-press.co.uk