Insights into selectin function from knockout mice.
The development of animal models through gene targeting was very useful to the selectin field. Selectins are found on endothelium, platelets and leukocytes and, they mediate adhesion among these cell types. The removal of a single selectin gene taught us that P-selectin on the vessel wall mediates leukocyte rolling in the absence of inflammation and that all three selectins contribute to leukocyte rolling during inflammation. Similarly, P-selectin is responsible for early neutrophil recruitment while the other selectins contribute in later stages. The knockout animals also confirmed the important role of L-selectin in lymphocyte homing. Removal of both endothelial selectins uncovered the hidden importance of E-selectin in leukocyte homeostasis and showed that the endothelial selectins were as important for leukocyte extravasation as the leukocyte beta 2 integrins. The submission of selectin-deficient mice to models of various human diseases can provide invaluable information on conditions in which an anti-selectin therapy may prove beneficial.
Frenette
P S
PS
Center for Blood Research, Boston, MA 02114, USA. frenette@cbr.med.harvard.edu
Wagner
D D
DD
D000818:Animals; D001161:Arteriosclerosis / Q000503:physiopathology; D019040:E-Selectin / Q000502:physiology; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000503:physiopathology; D019041:L-Selectin / Q000502:physiology; D008581:Meningitis / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D019007:P-Selectin / Q000502:physiology; D019087:Selectins / Q000502:physiology*
D019040:E-Selectin; D019007:P-Selectin; D019087:Selectins; D019041:L-Selectin