CD59 signaling and membrane pores drive Syk-dependent erythrocyte necroptosis.

Mature erythrocytes (red blood cells (RBCs)) undergo the programmed cell death (PCD) pathway of necroptosis in response to bacterial pore-forming toxins (PFTs) that target human CD59 (hCD59) but not hCD59-independent PFTs. Here, we investigate the biochemical mechanism of RBC necroptosis with a focus on the mechanism of induction and the minimal requirements for such RBC death. Binding or crosslinking of the hCD59 receptor led to Syk-dependent induction of vesiculated morphology (echinocytes) that was associated with phosphorylation of Band 3 and was required for Fas ligand (FasL) release. FasL-dependent phosphorylation of receptor-interacting protein kinase 1 (RIP1) in combination with plasma membrane pore formation was required for execution of RBC necroptosis. RIP1 phosphorylation led to the phosphorylation of RIP3, which was also critical for RBC necroptosis. Notably, RBC necroptosis was mediated by FasL and not by other candidate inducers, including tumor necrosis factor alpha (TNF-α) and TNF-related apoptosis-inducing ligand (TRAIL). Other types of RBC damage, such as eryptotic damage, failed to induce necroptosis when combined with hCD59 crosslinking. This work sheds light on the requirements for this recently discovered PCD in RBCs and provides a clear picture of the biochemical mechanism of induction of RBC necroptosis.

The important and diverse roles of antibodies in the host response to Borrelia infections.

Antibodies are of critical importance in the host response to tick-borne Borrelia species that cause relapsing fever and Lyme disease. Recent studies on the role of various B cell subsets in the host response to Borrelia, complement-independent, bactericidal antibodies, and diagnostics led to this review that focuses on the array of functions that antibodies to Borrelia can perform.

A Nonsurgical Method for the Placement of Transpyloric (Nasoenteric) Feeding Tubes Using Fluoroscopic Guidance in Dogs.

Transpyloric tube feeding is a commonly used form of nutritional support when patients are unable to tolerate oral or gastric feeding. Although nasoenteric placement of transpyloric feeding tubes is usually accomplished in humans, anatomic variations in laboratory species have necessitated surgical laparotomy for transpyloric tube placement. We have developed a reliable fluoroscopic technique for the nonsurgical placement of transpyloric feeding tubes in dogs. This technique was developed in an experimental setting and currently is being used in the treatment of canine patients at the Auburn University College of Veterinary Medicine Small Animal Clinic. After nasal passage of a weighted 8-French feeding tube with stylet into the stomach, dogs are placed in sternal recumbency, and the tube is advanced toward right side of the fundus under fluoroscopic visualization. The animal is then placed in left lateral recumbency, and the stomach is insufflated with 20-30 ml/kg air through the tube. The pylorus is visualized as air passes from the stomach into the proximal small intestine, and the tube is advanced across the pylorus and into the proximal intestine. Placement has been successful in anesthetized and awake animals and in dogs with a variety of illnesses. Complications include bile leakage from the externalized opening of the tube, with subsequent cellulitis and retrograde movement of the tube when placement is proximal to the caudal duodenal flexure. This technique can be used in clinical veterinary medicine and nutritional research studies involving canine models and avoids abdominal surgery for the placement of intestinal feeding tubes.