Blood
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Comparative Study
Increased soluble interleukin-1 type II receptor concentrations in postoperative patients and in patients with sepsis syndrome.
Plasma interleukin-1 (IL-1) activity is modulated in part through the simultaneous appearance of several inhibitors of IL-1 action, including interleukin-1 receptor antagonist (IL-1ra) and the soluble IL-1 type II receptor (IL-1RII). However, little is known concerning the plasma appearance of these inhibitors in patients following operative trauma or those with sepsis syndrome. In the present report, plasma IL-1beta, IL-1ra, and soluble IL-1RI and IL-1RII concentrations were evaluated in 118 patients with sepsis syndrome or after elective operative trauma. ⋯ Plasma IL-1RI concentrations decreased in all postoperative patients in the first 24 hours after surgery. We conclude that both plasma IL-1ra and soluble IL-1RII concentrations often increase in sepsis and following some operative trauma. Less severe operative trauma increases the plasma concentration of only IL-1ra, whereas both IL-1ra and soluble IL-1RII are increased in patients with sepsis syndrome or following thoraco-abdominal aneurysm repair.
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Co-localization of blood platelets and granulocytes at sites of hemostasis and inflammation has triggered an intense interest in possible interactions between these cellular processes and induction of vessel wall injury. Leukocyte adhesion to endothelial cells decreases with increasing shear and is dependent on an initial rolling phase mediated by selectins. We hypothesized that flow-dependent platelet adhesion at an injured vessel wall will lead to P-selectin expression by platelets, thus mediating leukocyte co-localization. ⋯ Studies with specific antibodies showed that the platelet-dependent neutrophil adhesion was selectin-mediated. Inhibition of P-selectin caused a marked inhibition of adhesion at high shear stress, whereas the role of leukocyte L-selectin was less pronounced. beta2-Integrin-blocking antibodies inhibited static neutrophil adhesion. fMLP induced L-selectin shedding from leukocytes, resulting in decreased leukocyte adhesion. In conclusion, platelet-dependent hemostasis at the ECM appears to be a powerful intermediate in neutrophil-vessel wall interactions at shear stresses that normally do not allow neutrophil adhesion to intact endothelium.
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Spur cell anemia may occur in severe liver disease including alcoholic cirrhosis. Spur cell anemia red blood cells (RBCs) have a characteristic morphology, with irregular projections, an increased ratio of membrane cholesterol (Ch) to phospholipid, evidence of oxidative damage, and shortened survival resulting in hemolytic anemia. Normal RBCs may acquire many of the features of spur cells either by transfusion into a spur cell patient or in an in vitro model system that loads the RBC membrane with Ch relative to phospholipid by means of Ch-rich, phospholipid-Ch sonicates. ⋯ Similar LAT assay results were obtained using [14C]palmitoyl LPC as the precursor. We conclude that Ch-loading of RBC membranes results in inhibition of LAT in the cell-free system in vitro and may account for the inhibited phospholipid repair in Ch-loaded intact RBCs in vitro and in spur cell anemia RBCs in vivo. Decreased ability to replace peroxidized membrane fatty acid by this metabolic pathway may contribute to the hemolytic process in spur cell anemia.
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Iron-regulatory proteins (IRP1 and IRP2) are RNA-binding proteins that bind to stem-loop structures known as iron-responsive elements (IREs). IREs are located in the 5'- or 3'-untranslated regions (UTRs) of specific mRNAs that encode proteins involved in iron homeostasis. The binding of IRPs to 5' IREs represses translation of the mRNA, whereas the binding of IRPs to 3' IREs stabilizes the mRNA. ⋯ The increase in IRE binding activity of IRP1 was coincident with the translational repression of ferritin synthesis. Transferrin receptor (TfR) mRNA levels were increased in cells treated with NO.-generating compounds, but not in cytokine- and LPS-treated cells. Our data indicate that IRP1 and IRP2 are differentially regulated by NO. in rat hepatoma cells, suggesting a role for IRP1 in the regulation of iron homeostasis in vivo during hepatic inflammation.