ABSTRACT
Addressing the mononuclear phagocyte system (MPS) and macrophage M1/M2 activation is important in diagnosing hematological disorders and inflammatory pathologies and designing therapeutic tools. CSF1R is a reliable marker to identify all circulating MPS cells and tissue macrophages in humans using a single surface protein. CSF1R permits the quantification and isolation of monocyte and dendritic cell (DC) subsets in conjunction with CD14, CD16, and CD1c and is stable across the lifespan and sexes in the absence of overt pathology. Beyond cell detection, measuring M1/M2 activation in humans poses challenges due to response heterogeneity, transient signaling, and multiple regulation steps for transcripts and proteins. MPS cells respond in a conserved manner to M1/M2 pathways such as interleukin-4 (IL-4), steroids, interferon-γ (IFNγ), and lipopolysaccharide (LPS), for which we propose an ad hoc modular gene expression tool. Signature analysis highlights macrophage activation mosaicism in experimental samples, an emerging concept that points to mixed macrophage activation states in pathology.
Subject(s)
Macrophage Activation , Macrophages , Receptors, Granulocyte-Macrophage Colony-Stimulating Factor , Humans , Macrophage Activation/genetics , Macrophages/metabolism , Macrophages/immunology , Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/genetics , Interferon-gamma/metabolism , Lipopolysaccharides/pharmacology , Female , Mosaicism , Male , Monocytes/metabolism , Lipopolysaccharide Receptors/metabolism , Interleukin-4/metabolism , Dendritic Cells/metabolism , Dendritic Cells/immunology , Receptors, IgG/metabolism , Receptors, IgG/genetics , Antigens, CD1/metabolism , Antigens, CD1/genetics , Mononuclear Phagocyte System/metabolism , Glycoproteins , Receptor, Macrophage Colony-Stimulating FactorABSTRACT
Older people are increasingly being referred for consideration for pancreas transplantation (PT). We investigated the outcomes after PT in our older recipient cohort. A prospectively maintained database was interrogated. The cohort was analysed for associations between outcome and older recipient age. A total of 444 transplants were performed in patients aged 23-54 years and 83 transplants in patients aged 55-67 years. There was no difference in death-censored pancreas or kidney graft survival between the groups. Patient death was associated with older recipient age (HR 1.63 per 10-year increase). In multivariate Cox regression, risk of mortality was also associated with post-transplant myocardial infarction (HR 7.25, P = 0.006), pancreas failure (HR 1.91, P = 0.003) and kidney failure (HR 3.55, P < 0.001). About 40% of recipients who died in the first year post-transplant suffered early graft loss. Those alive at a year post-transplant had inferior survival if they had lost their kidney graft (P < 0.001). Mortality is higher in older patients and is strongly associated with pancreas and kidney graft failure. This suggests that pancreas transplantation is feasible in older recipients, and careful selection of donor organs is important to optimize survival.
