Expression of the Myxoma Virus Tumor Necrosis Factor Receptor Homologue and M11L Genes Is Required to Prevent Virus-Induced Apoptosis in Infected Rabbit T Lymphocytes

AbstractMyxoma virus is a leporipoxvirus that causes a highly lethal virulent disease known as myxomatosis in the European rabbit. An important aspect of myxoma virus pathogenesis is the ability of the virus to productively infect lymphocytes and spread to secondary sites via lymphatic channels. We investigated the infection of the CD4+T lymphoma cell line RL-5 with myxoma virus and Shope fibroma virus, a related but benign leporipoxvirus, and observed that myxoma virus, but not Shope fibroma virus, was able to productively infect RL-5 cells. We also discovered that infection of RL-5 cells with Shope fibroma virus or attenuated myxoma virus mutants containing disruptions in either the T2 or the M11L gene resulted in the rapid induction of DNA fragmentation, followed by morphological changes and loss in cell integrity characteristic of cell death by apoptosis. Purified exogenous T2 protein was unable to prevent apoptosis, suggesting that T2 functions intracellularly. Thus, myxoma virus T2, originally described as a secreted homologue of the tumor necrosis factor receptor, and M11L, a novel transmembrane species with no known cellular homologue, function to extend virus host range for replication in rabbit T lymphocytes through the inhibition of apoptosis in infected T lymphocytes

Cardiopulmonary Bypass Using Argatroban as an Anticoagulant for a 6.0-kg Pediatric Patient

A patient was born with transposition of the great arteries, double-outlet right ventricle, interrupted aortic arch, and a ventricular septal defect and underwent a Damus–Kaye–Stansel procedure with a modified Blalock–Taussig shunt at 14 days old. Three months later, this patient presented with hypoxia and bradycardia was found to have a thrombus present in the main pulmonary artery extending to right pulmonary artery. After initiation of thrombolytic therapy, the patient became severely hypoxic and required the institution of extracorporeal membrane oxygenation. As the result of unknown heparin resistance independent of adequate antithrombin III levels, argatroban therapy was used to achieve desired anticoagulation. The patient was taken to the operating room and converted to conventional cardiopulmonary bypass once adequate activated clotting times were achieved using argatroban. This case report summarizes the use of argatroban as an anticoagulant for a 6.0-kg pediatric patient undergoing cardiopulmonary bypass

Argatroban Usage For Anticoagulation for ECMO on a Post-Cardiac Patient with Heparin-Induced Thrombocytopenia

We report a post-Norwood Stage I patient requiring ECMO support using Argatroban as an anticoagulant following diagnosis of heparin-induced thrombocytopenia (HIT). A 2.6 kg female was born with hypoplastic left heart syndrome and underwent a Norwood Stage I operation on day 4 of life. The patient weaned off cardiopulmonary bypass with no complications and was routinely placed on a ventricular assist device (VAD) for 3 days. Heparin was infused at a rate of 16–32 IU/kg/h to maintain an ACT of 160–180 seconds. Two days after VAD termination, the patient was placed on continuous veno– veno hemofiltration (CVVH). Shortly after CVVH, the patient was diagnosed with HIT and placed on an Argatroban infusion. Five days later, a VAD and subsequent ECMO was used because of decreasing left ventricular function, gross body edema, and poor renal function. This case report summarizes the use of Argatroban during VAD and ECMO support for a patient diagnosed with HIT

Soluble CD40 ligand accumulates in stored blood components, primes neutrophils through CD40, and is a potential cofactor in the development of transfusion-related acute lung injury

Transfusion-related acute lung injury (TRALI) is a form of posttransfusion acute pulmonary insufficiency that has been linked to the infusion of biologic response modifiers (BRMs), including antileukocyte antibodies and lipids. Soluble CD40 ligand (sCD40L) is a platelet-derived proinflammatory mediator that accumulates during platelet storage. We hypothesized that human polymorpho-nuclear leukocytes (PMNs) express CD40, CD40 ligation rapidly primes PMNs, and sCD40L induces PMN-mediated cytotoxicity of human pulmonary microvascular endothelial cells (HMVECs). Levels of sCD40L were measured in blood components and in platelet concentrates (PCs) implicated in TRALI or control PCs that did not elicit a transfusion reaction. All blood components contained higher levels of sCD40L than fresh plasma, with apheresis PCs evidencing the highest concentration of sCD40L followed by PCs from whole blood, whole blood, and packed red blood cells (PRBCs). PCs implicated in TRALI reactions contained significantly higher sCD40L levels than control PCs. PMNs express functional CD40 on the plasma membrane, and recombinant sCD40L (10 ng/mL-1 μg/mL) rapidly (5 minutes) primed the PMN oxidase. Soluble CD40L promoted PMN-mediated cytotoxicity of HMVECs as the second event in a 2-event in vitro model of TRALI. We concluded that sCD40L, which accumulates during blood component storage, has the capacity to activate adherent PMNs, causing endothelial damage and possibly TRALI in predisposed patients