Translational research : the journal of laboratory and clinical medicine
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Macrophages play critical roles in homeostatic maintenance of the myocardium under normal conditions and in tissue repair after injury. In the steady-state heart, resident cardiac macrophages remove senescent and dying cells and facilitate electrical conduction. In the aging heart, the shift in macrophage phenotype to a proinflammatory subtype leads to inflammaging. ⋯ Infarct macrophages exhibit a proinflammatory M1 phenotype early and become polarized toward an anti-inflammatory M2 phenotype later post-MI. Although this classification system is oversimplified and needs to be refined to accommodate the multiple different macrophage subtypes that have been recently identified, general concepts on macrophage roles are independent of subtype classification. This review summarizes current knowledge about cardiac macrophage origins, roles, and phenotypes in the steady state, with aging, and after MI, as well as highlights outstanding areas of investigation.
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Increasing experimental and clinical evidence has revealed a critical role for myeloid cells in the development and progression of cancer. The ability of monocytes and macrophages to regulate inflammation allows them to manipulate the tumor microenvironment to support the growth and development of malignant cells. Recent studies have shown that macrophages can exist in several functional states depending on the microenvironment they encounter in the tissue. ⋯ In the context of tumors, classically activated or M1 macrophages driven by interferon-gamma support antitumor immunity while alternatively activated or M2 macrophages generated in part from interleukin-4 exposure hinder antitumor immunity by suppressing cytotoxic responses against a tumor. In this review, we discuss the role that the functional phenotype of a macrophage population plays in tumor development. We will then focus specifically on how macrophages and myeloid cells regulate the tumor response to radiation therapy.
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Hypertension is a multifactorial disease involving the nervous, renal, and cardiovascular systems. Macrophages are the most abundant and ubiquitous immune cells, placing them in a unique position to serve as key mediators between these components. The polarization of macrophages confers vast phenotypic and functional plasticity, allowing them to act as proinflammatory, homeostatic, and anti-inflammatory agents. ⋯ In hypertension, the neuroimmuno axis results in synchronization of macrophage mobilization from immune cell reservoirs and their chemotaxis, via increased expression of chemoattractants, to end organs critical in the development of hypertension. This complicated system is largely coordinated by the dichotomous actions of the autonomic neuronal and non-neuronal activation of cholinergic, adrenergic, and neurohormonal receptors on macrophages, leading to their ability to "switch" between phenotypes at sites of active inflammation. Data from experimental models and human studies are in concordance with each other and support a central role for macrophage polarization in the pathogenesis of hypertension.