RAGE-dependent VCAM-1 expression in the lung endothelium mediates IL-33-induced allergic airway inflammation.

BACKGROUND: The receptor for advanced glycation endproducts (RAGE) has been implicated as a critical molecule in the pathogenesis of experimental asthma/allergic airway inflammation (AAI). It has been previously shown that RAGE acts both upstream of interleukin-33 (IL-33) release and downstream of IL-33 release via RAGE-dependent IL-33-induced accumulation of type 2 innate lymphoid cells (ILC2s) in the lungs, which perpetuate type 2 inflammation and mucus metaplasia. However, the mechanism by which RAGE mediates downstream IL-33-induced type 2 inflammatory responses is unknown. OBJECTIVE: This study tested the hypothesis that ILC2s are recruited to the lungs via RAGE-dependent vascular cell adhesion molecule 1 (VCAM-1) expression on lung endothelial cells. METHODS: House dust mite extract, Alternaria alternata extract, or rIL-33 was used to induce AAI/VCAM-1 expression in wild-type (WT) and RAGE-knockout (RAGE-KO) mice. Intravenous (i.v.) anti-VCAM-1 or intraperitoneal (i.p.) ß7 blocking antibody administration was used to determine the role of VCAM-1 in IL-33-induced AAI. RESULTS: Enhanced VCAM-1 expression in the lungs by HDM, AA, or rIL-33 exposure was found to be RAGE-dependent. In addition, stimulation of primary mouse lung endothelial cells with IL-33 induced VCAM-1 expression in WT, but not RAGE-KO cells. Administration of VCAM-1 and ß7-integrin blocking antibodies reduced IL-33-induced eosinophilic inflammation, mucus metaplasia, and type 2 inflammatory responses. CONCLUSION: This study demonstrates that allergen- and cytokine-induced VCAM-1 expression is RAGE-dependent and contributes to lung ILC2 accumulation and downstream eosinophilic inflammation, mucus metaplasia, and type 2 inflammatory responses.

[Postoperative total parenteral feeding with a carbohydrate mixture (autor's transl)]. / Postoperative totale parenterale Ernährung unter Verwendung einer Kohlenhydratmischung

After gastric operations, patients were fed completely by the parenteral route. Aminoacids, caloric nutrients and electrolytes were infused simultaneously and continuously 24 hours daily until the fourth postoperative day. The daily supply of aminoacids amounted to 80 g. Glucose, fructose and xylite in equal proportions were used to supply calories. The total daily amount was 605 g. The important electrolytes were contained in the infusion solutions in amounts corresponding to basic requirement. The results of the investigation confirmed that patients can be successfully nourished parenterally after extensive operations with the combined daily additives we have selected.

[Metabolic behavior in total parenteral nutrition during the postoperative phase]. / Stoffwechselverhalten bei totaler parenteraler Ernährung in der postoperativen Phase

In patients who had undergone gastric operation, total postoperative parenteral nutrition was effected using a combination of two infusion solutions having complementary constituents. 80 g L-amino acids and about 2,500 kcal in the form of a glucose-levulose-xylitol mixture together with electrolytes and trace elements were infused daily. Metabolic parameters, serum levels and the concentrations of the most important administered substances excreted in the urine were determined every day at the same time. The 1:1:1 glucose-levulose-xylitol ratio of the caloric carrier proved to be a favourable combination with respect to metabolic behaviour and the necessary daily supply of calories. The basic electrolyte requirement of the patients was to a large extent met by the quantities contained in the solutions.