Modulation of macrophage phagocytosis in vitro-A role for cholinergic stimulation?

Acetylcholine is synthetized and released from neural cells, but also by non-neuronal cells such as epithelial cells or keratinocytes. Cholinergic agonists enhance the phagocytosis of zymosan particles in primary peritoneal macrophages. The aim of this study was to investigate the effect of carbachol stimulation on phagocytosis in a macrophage cell line using microspheres. The murine cell line MH-S was used in a phagocytosis assay with fluorescent latex beads. The amount of the ingested beads was determined using flow cytometry. Gene expression was investigated using polymerase chain reaction. Gene expression of the muscarinic receptors M1, M3, M4 and M5 but not M2 was found. Carbachol slightly increased the phagocytosis of microspheres in the macrophages. A co-stimulation using lipopolysaccharide and carbachol did not increase the effect of lipopolysaccharide alone. In conclusion, cholinergic stimulation in vitro only moderately modulates the phagocytosis of microspheres. M2 might have a role in stimulation of macrophage phagocytosis.

Targeting the non-neuronal cholinergic system in macrophages for the management of infectious diseases and cancer: challenge and promise.

Macrophages represent key players of the immune system exerting highly effective defense mechanisms against microbial infections and cancer that include phagocytosis and programmed cell removal. Recent findings highlight the relevance of the non-neuronal cholinergic system for the regulation of macrophage function that opens promising new concepts for the treatment of infectious diseases and cancer. This mini review summarizes our present knowledge on this topic and gives an outlook on future developments.

Immunohistochemical expression of nuclear factor erythroid-2-related factor 2 and heme oxygenase 1 in normal bovine lung and bovine lung infected with Mannheimia haemolytica.

Mannheimia haemolytica is an important cause of pneumonia in feedlot cattle. Nuclear factor erythroid-2-related factor 2 (Nrf2) is a redox-sensitive transcription factor responsible for the induction of antioxidant enzymes, such as heme oxygenase 1 (HO-1), within the lung. The expression of Nrf2 and HO-1 was immunohistochemically evaluated in 4 calves 24 h after experimental infection with M. haemolytica. Calves receiving normal saline served as controls. In the infected lungs, cytoplasmic Nrf2 expression was high in macrophages and bronchioles and low in alveolar epithelium, whereas nuclear expression was high in endothelial cells, macrophages, and bronchioles and lowest in alveolar epithelium. Normal lung samples displayed only faint Nrf2 cytoplasmic staining within bronchiolar epithelium. Expression of HO-1 was detected within the cytoplasm of macrophages and bronchiolar epithelial cells in all infected lung samples, whereas normal lungs displayed only weak cytoplasmic staining in bronchiolar epithelial cells. These findings suggest that bronchiolar epithelial cells and macrophages up-regulate Nrf2 expression early in the course of infection, which results in increased expression of HO-1 within these cells.

Mannheimia haemolytica est une cause importante de pneumonie chez les bovins en parc d'engraissement. Le facteur érythroïde-2 nucléaire apparenté au facteur 2 (Nrf2) est un facteur transcriptionnel sensible au potentiel redox responsable de l'induction d'enzymes antioxidants, tel que l'hème oxygénase 1 (HO-1), dans le poumon. L'expression de Nrf2 et HO-1 fut évaluée par épreuve immunohistochimique chez quatre veaux 24 h après une infection expérimentale avec M. haemolytica. Les veaux témoins ont reçu de la saline. Dans les poumons infectés, l'expression cytoplasmique de Nrf2 était élevée dans les macrophages et les bronchioles et faible dans l'épithélium alvéolaire, alors que l'expression nucléaire était élevée dans les cellules endothéliales, macrophages et bronchioles, et à son plus faible dans l'épithélium alvéolaire. Les échantillons de poumons normaux montraient seulement une faible coloration cytoplasmique pour Nrf2 dans l'épithélium des bronchioles. L'expression de HO-1 fut détectée dans le cytoplasme des macrophages et des cellules épithéliales des bronchioles de tous les échantillons de poumons infectés, alors que les échantillons de poumons normaux ne montraient qu'une faible coloration cytoplasmique dans les cellules épithéliales des bronchioles. Ces données suggèrent que les cellules épithéliales des bronchioles et les macrophages régulent à la hausse l'expression de Nrf2 tôt lors de l'infection, ce qui résulte en une expression augmentée d'HO-1 à l'intérieur de ces cellules.(Traduit par Docteur Serge Messier).