Browsing by MeSH term "Receptors, Granulocyte-Macrophage Colony-Stimulating Factor"
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Publication Resident and recruited macrophages differentially contribute to cardiac healing after myocardial ischemia.(eLife Sciences Publications, 2024-05-22) Weinberger, Tobias; Denise, Messerer; Joppich, Markus; Fischer, Maximilian; Garcia Rodriguez, Clarisabel; Kumaraswami, Konda; Wimmler, Vanessa; Ablinger, Sonja; Räuber, Saskia; Fang, Jiahui; Liu, Lulu; Liu, Wing Han; Winterhalter, Julia; Lichti, Johannes; Thomas, Lukas; Esfandyari, Dena; Percin, Guelce; Matin, Sandra; Hidalgo, Andres; Waskow, Claudia; Engelhardt, Stefan; Todica, Andrei; Zimmer, Ralf; Pridans, Clare; Gomez Perdiguero, Elisa; Schulz, ChristianCardiac macrophages are heterogenous in phenotype and functions, which has been associated with differences in their ontogeny. Despite extensive research, our understanding of the precise role of different subsets of macrophages in ischemia/reperfusion (I/R) injury remains incomplete. We here investigated macrophage lineages and ablated tissue macrophages in homeostasis and after I/R injury in a CSF1R-dependent manner. Genomic deletion of a fms-intronic regulatory element (FIRE) in the Csf1r locus resulted in specific absence of resident homeostatic and antigen-presenting macrophages, without affecting the recruitment of monocyte-derived macrophages to the infarcted heart. Specific absence of homeostatic, monocyte-independent macrophages altered the immune cell crosstalk in response to injury and induced proinflammatory neutrophil polarization, resulting in impaired cardiac remodeling without influencing infarct size. In contrast, continuous CSF1R inhibition led to depletion of both resident and recruited macrophage populations. This augmented adverse remodeling after I/R and led to an increased infarct size and deterioration of cardiac function. In summary, resident macrophages orchestrate inflammatory responses improving cardiac remodeling, while recruited macrophages determine infarct size after I/R injury. These findings attribute distinct beneficial effects to different macrophage populations in the context of myocardial infarction.Publication Should We Open Fire on Microglia? Depletion Models as Tools to Elucidate Microglial Role in Health and Alzheimer's Disease.(2021-09-08) Romero-Molina, Carmen; Navarro, Victoria; Jimenez, Sebastian; Muñoz-Castro, Clara; Sanchez-Mico, Maria V; Gutierrez, Antonia; Vitorica, Javier; Vizuete, MarisaMicroglia play a critical role in both homeostasis and disease, displaying a wide variety in terms of density, functional markers and transcriptomic profiles along the different brain regions as well as under injury or pathological conditions, such as Alzheimer's disease (AD). The generation of reliable models to study into a dysfunctional microglia context could provide new knowledge towards the contribution of these cells in AD. In this work, we included an overview of different microglial depletion approaches. We also reported unpublished data from our genetic microglial depletion model, Cx3cr1CreER/Csf1rflx/flx, in which we temporally controlled microglia depletion by either intraperitoneal (acute model) or oral (chronic model) tamoxifen administration. Our results reported a clear microglial repopulation, then pointing out that our model would mimic a context of microglial replacement instead of microglial dysfunction. Next, we evaluated the origin and pattern of microglial repopulation. Additionally, we also reviewed previous works assessing the effects of microglial depletion in the progression of Aβ and Tau pathologies, where controversial data are found, probably due to the heterogeneous and time-varying microglial phenotypes observed in AD. Despite that, microglial depletion represents a promising tool to assess microglial role in AD and design therapeutic strategies.Publication Tissue-resident macrophages regulate lymphatic vessel growth and patterning in the developing heart.(The Company of Biologists, 2021-01) Cahill, Thomas J; Sun, Xin; Ravaud, Christophe; Villa del Campo, Cristina; Klaourakis, Konstantinos; Lupu, Irina-Elena; Lord, Allegra M; Browne, Cathy; Jacobsen, Sten Eirik W; Greaves, David R; Jackson, David G; Cowley, Sally A; James, William; Choudhury, Robin P; Vieira, Joaquim Miguel; Riley, Paul R; British Heart Foundation; BHF Oxbridge Centre of Regenerative Medicine; Wellcome Trust; BHF Intermediate Basic Science Research; British Council. BIRAX (British Israel Research and Academic Exchange Partnership); Fondation LeducqMacrophages are components of the innate immune system with key roles in tissue inflammation and repair. It is now evident that macrophages also support organogenesis, but few studies have characterized their identity, ontogeny and function during heart development. Here, we show that the distribution and prevalence of resident macrophages in the subepicardial compartment of the developing heart coincides with the emergence of new lymphatics, and that macrophages interact closely with the nascent lymphatic capillaries. Consequently, global macrophage deficiency led to extensive vessel disruption, with mutant hearts exhibiting shortened and mis-patterned lymphatics. The origin of cardiac macrophages was linked to the yolk sac and foetal liver. Moreover, the Cx3cr1 + myeloid lineage was found to play essential functions in the remodelling of the lymphatic endothelium. Mechanistically, macrophage hyaluronan was required for lymphatic sprouting by mediating direct macrophage-lymphatic endothelial cell interactions. Together, these findings reveal insight into the role of macrophages as indispensable mediators of lymphatic growth during the development of the mammalian cardiac vasculature.