Blood
-
Several pieces of evidence are reported for the accumulation of activated neutrophils in ischemic and reperfused tissues leading to the transformation of the ischemic tissue into an inflammatory territory and to an enhancement of tissue damages during reoxygenation. However, the molecular mechanisms responsible for these observations and the precise role played by endothelial cells in this process are still poorly understood. In this study, an in vitro model that mimics this situation was used to investigate the effects of hypoxia-incubated human umbilical vein endothelial cells (HUVEC) on polymorphonuclear leukocyte (PMN) functions. ⋯ We thus evidenced that free radicals but not elastase released from activated PMN coincubated with hypoxic HUVEC are involved in HUVEC injury. We conclude from these results that PMN activation is initiated by PMN adherence to hypoxic HUVEC. These observations indicate that hypoxic HUVEC may be partly responsible for neutrophil activation observed in ischemic tissues, which is part of the amplification process of tissue damage.
-
We explored in dogs the immunosuppressive properties of 450 cGy total body irradiation (TBI) delivered from two opposing 60Co sources, as assessed by the criterion of successful engraftment of allogeneic genotypically DLA-identical littermate marrow. Two questions were asked in this study. Firstly, does dose rate affect the immunosuppressive effect of TBI when administered in a single dose? Secondly, does fractionation alter the immunosuppression of TBI when delivered at a very fast dose rate? Dose rates studied included 7 and 70 cGy/min, and fractionation involved four fractions of 112.5 cGy each, with 6-hour minimum interfraction intervals. ⋯ A single dose of 450 cGy of TBI delivered at a rate of 70 cGy/min is significantly more immunosuppressive than the same total dose delivered at 7 cGy/min. Fractionated TBI at 70 cGy/min is significantly less immunosuppressive than single-dose TBI at 70 cGy/min and not significantly different from fractionated TBI administered at 7 cGy/min. Results are consistent with the notion that significant DNA repair in lymphoid cells is possible during interfraction intervals at the relatively high dose rate of 70 cGy/min.