Hypoxia reoxygenation-induced injury of cultured pulmonary microvessel endothelial cells

Abstract

Polymorphonuclear leukocyte (PMN) sequestration within the pulmonary microvasculature is known to occur in association with ischemia/reoxygenation (I/R). This sequestration is dependent on eicosanoids and reactive oxygen species. PMN sequestration within the lungs suggests that pulmonary microvascular endothelial cells (MECs) may in part regulate the I/R response. Simulating I/R, we examined the effect of hypoxia/reoxygenation (H/R) on pulmonary MECs in vitro, with and without PMNs. Significant cellular injury, assessed by 51Cr release, occurred upon reoxygenation of MECs (P < .01). Addition of PMNs to the H/R-injured monolayers did not increase MEC injury. Reoxygenation of MECs also resulted in increased thromboxane (Tx) B2 production compared to controls (P < .01). Inhibition of Tx secretion by aspirin reduced H/R-induced PMN adhesion to MECs (P < .01). Furthermore, H/R-induced increases in PMN-MEC adhesion were prevented by allopurinol and superoxide dismutase (P < .01). These data suggest that the pulmonary response to H/R is mediated by MEC generation of reactive oxygen radical species and Tx, which promotes increased PMN adhesion.

Taurine Protects Gut Barrier Function and Prevents Endothelial Cell Injury Induced by Ischaemia-Reperfusion

“…Several studies have shown that EC are resistant to hypoxia, requiring a prolonged period of reduced oxygen to induce cell death [32]. Yet ischaemia/reperfusion (I/R) induces cell death in human umbilical vein EC (HUVEC), human coronary artery EC, and pulmonary microvessel EC [33] [34] [35]. In agreement with previous findings our study demonstrates that hypoxia resulted in significantly increased intracellular Ca 2+ and ROS levels in HSVECs.…”

In vitro andin vivo impact of a new glycosphingolipid on neutrophils

“…4 and 5 and Table 2 are all in favour of strong inhibition by orally administered WILD20 of neutrophil tropism towards inflammation loci, whichever the agonist used, and they confirmed the well-known effect of LTB4 and PAF on leukocyte recruitment into inflamed tissues [173 . The effect of WILD20 on neutrophil tropism consequently led to evaluation of its possible impact on neutrophil adhesion to endothelial cells, considering the known relationship between oxidative processes, eicosanoids and sequestration in organ microvasculature [18,19]. Results are reported in Table 3; WILD20 reduced ICAM-1-related neutrophil adhesion to resting endothelial cells activated with TNFa at different times.…”

“…In fact, the oxidation of arachidonic acid in a superoxide-generating system leads to the generation of powerful chemoattractants [16]; also, sequestration processes into tissues are dependent on both eicosanoids and ROS [19].…”

Hypoxia, such as encountered at high altitude, promotes deep vein thrombosis in mice

“…In the majority of cases, hypoxia is followed by restoration of oxygen supply (i.e., reoxygenation). Hypoxia/reoxygenation (H/R), which is known to be harmful to tissues [8,9], is proposed to be an exacerbating factor for thrombus development in veins, although this causal relationship has not been directly proved. A crucial role of the reoxygenation phase in DVT can be suggested because thrombotic events frequently occur after landing [7,10].…”