Role of P-selectin in radiation-induced intestinal inflammatory damage

The aims of our study were to characterize the dose- and time-dependent cha nges in endothelial P-selectin expression and the role of this adhesion mol ecule as a mediator of radiation-induced inflammation. For that purpose, en dothelial P-selectin expression was measured by the radiolabeled antibody t echnique in control and irradiated mice at 2, 6, and 24 hr following abdomi nal irradiation with 4 or 10 Gy; leukocyte endothelial cell interactions we re assessed using intravital microscopy in intestinal venules following irr adiation at the aforementioned doses and times in C57BL/6 and P-selectin-de ficient mice. In wild-type mice, radiation induced a time- and dose-depende nt upregulation of P-selectin and a significant increase in the flux of rol ling leukocytes 2 hr after irradiation. Irradiation induced a significant i ncrease in leukocyte adhesion that was dose-dependent. Following irradiatio n, P-selectin-deficient mice did not show any increase in leukocyte rolling but did demonstrate a response in leukocyte adhesion similar to that of th e wild-type mice. Radiation-induced dose-dependent histological inflammator y damage that did not differ between P-selectin-deficient and wild-type mic e. We conclude that P-selectin is up-regulated following irradiation and is a key molecular determinant of leukocyte rolling but not leukocyte adhesio n in this inflammatory condition. Therefore, isolated neutralization of thi s adhesion molecule is not an effective means for preventing radiation-indu ced inflammation. (C) 2001 Wiley-Liss, Inc.