by Keyword: Monocytes
Rosell, Alejandro, Krygowska, Agata Adelajda, Perez, Marta Alcon, Cuesta, Cristina, Voisin, Mathieu-Benoit, de Paz, Juan, Sanz-Fraile, Hector, Rajeeve, Vinothini, Carreras-Gonzalez, Ana, Berral-Gonzalez, Alberto, Swinyard, Ottilie, Gabande-Rodriguez, Enrique, Downward, Julian, Alcaraz, Jordi, Anguita, Juan, Garcia-Macias, Carmen, Cutillas, Pedro R, Cutillas, Pedro R, Sanchez, Esther Castellano, (2025). RAS-p110α signalling in macrophages is required for effective inflammatory response and resolution of inflammation Elife 13, RP94590 
Macrophages are crucial in the body's inflammatory response, with tightly regulated functions for optimal immune system performance. Our study reveals that the RAS-p110 alpha signalling pathway, known for its involvement in various biological processes and tumourigenesis, regulates two vital aspects of the inflammatory response in macrophages: the initial monocyte movement and later-stage lysosomal function. Disrupting this pathway, either in a mouse model or through drug intervention, hampers the inflammatory response, leading to delayed resolution and the development of more severe acute inflammatory reactions in live models. This discovery uncovers a previously unknown role of the p110 alpha isoform in immune regulation within macrophages, offering insight into the complex mechanisms governing their function during inflammation and opening new avenues for modulating inflammatory responses.
JTD Keywords: Actin, Cytoskeleton, Differential expression analysis, Inflammation, Inhibition, Macrophages, Monocytes, Nf-kappa-b, P110-alpha isoform, Pathwa, Ras, Ras-p110 alph, Recruitment
Hervera, A., De Virgiliis, F., Palmisano, I., Zhou, L., Tantardini, E., Kong, G., Hutson, T., Danzi, M. C., Perry, R. B. T., Santos, C. X. C., Kapustin, A. N., Fleck, R. A., Del Río, J. A., Carroll, T., Lemmon, V., Bixby, J. L., Shah, A. M., Fainzilber, M., Di Giovanni, S., (2018). Reactive oxygen species regulate axonal regeneration through the release of exosomal NADPH oxidase 2 complexes into injured axons Nature Cell Biology 20, (3), 307-319
Reactive oxygen species (ROS) contribute to tissue damage and remodelling mediated by the inflammatory response after injury. Here we show that ROS, which promote axonal dieback and degeneration after injury, are also required for axonal regeneration and functional recovery after spinal injury. We find that ROS production in the injured sciatic nerve and dorsal root ganglia requires CX3CR1-dependent recruitment of inflammatory cells. Next, exosomes containing functional NADPH oxidase 2 complexes are released from macrophages and incorporated into injured axons via endocytosis. Once in axonal endosomes, active NOX2 is retrogradely transported to the cell body through an importin-β1–dynein-dependent mechanism. Endosomal NOX2 oxidizes PTEN, which leads to its inactivation, thus stimulating PI3K–phosporylated (p-)Akt signalling and regenerative outgrowth. Challenging the view that ROS are exclusively involved in nerve degeneration, we propose a previously unrecognized role of ROS in mammalian axonal regeneration through a NOX2–PI3K–p-Akt signalling pathway.
JTD Keywords: Adult neurogenesis, Endocytosis, Exocytosis, Monocytes and macrophages, Stress signalling
Navarro, M., Pu, F., Hunt, J. A., (2012). The significance of the host inflammatory response on the therapeutic efficacy of cell therapies utilising human adult stem cells Experimental Cell Research 318, (4), 361-370
Controlling the fate of implanted hMSCs is one of the major drawbacks to be overcome to realize tissue engineering strategies. In particular, the effect of the inflammatory environment on hMSCs behaviour is poorly understood. Studying and mimicking the inflammatory process in vitro is a very complex and challenging task that involves multiple variables. This research addressed the questions using in vitro co-cultures of primary derived hMSCs together with human peripheral blood mononucleated cells (PBMCs); the latter are key agents in the inflammatory process. This work explored the in vitro phenotypic changes of hMSCs in co-culture direct contact with monocytes and lymphocytes isolated from blood using both basal and osteogenic medium. Our findings indicated that hMSCs maintained their undifferentiated phenotype and pluripotency despite the contact with PBMCs. Moreover, hMSCs demonstrated increased proliferation and were able to differentiate specifically down the osteogenic lineage pathway. Providing significant crucial evidence to support the hypothesis that inflammation and host defence mechanisms could be utilised rather than avoided and combated to provide for the successful therapeutic application of stem cell therapies.
JTD Keywords: Co-culture, Inflammation, Mesenchymal stem cells, Monocytes, Osteoblasts
