The mononuclear phagocyte system (MPS) is an ensemble of heterogeneous cells comprising circulating monocytes, macrophages, and dendritic cells. Immunohistochemistry is a valuable technique to detect, quantify, and localize MPS cells in tissues, but a comprehensive characterization of MPS cells in normal tissues of mice is lacking to date. The aim of this study was to immunohistochemically characterize MPS cells in a set of murine healthy tissues and in a subset of representative disease states. Sections of healthy tissues obtained from 21 C57BL/6J and C57BL/6N mice and sections of inflammatory (necrosuppurative hepatitis and Pneumocystis murina–associated pneumonia) and experimentally induced neoplastic conditions (human fibrosarcoma xenograft and mammary carcinoma syngraft) were immunolabeled with a panel of MPS markers, including IBA1, F4/80, macrophage receptor with collagenous structure (MARCO), CD206, arginase 1, Ym1, induced nitric oxide synthase, heme-oxygenase 1 (HO-1), and class II major histocompatibility complex (MHC-II). For each tissue, the amount, morphology, location, and immunolabeling intensity of positive cells were evaluated using semi-quantitative scores. Results highlighted the morphological and immunophenotypic heterogeneity of murine MPS cells. The panel of antibodies used allowed for discrimination of different cell populations across the examined tissues based on immunophenotype, microanatomical location, and morphology, providing useful morphological and functional clues on MPS cells in both physiological and diseased conditions. The results of this study provide a valuable reference regarding the amount, morphology, microanatomical location, and immunophenotype of MPS subsets in healthy murine tissues. In addition, it highlights the plasticity of these cells in inflammatory and neoplastic settings, underscoring the importance of a comprehensive characterization of MPS cells in physiological and disease states.
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