Clear Cell Debris Research Articles

Modulators of Macrophage Polarization Influence Healing of the Infarcted Myocardium.

To diminish heart failure development after acute myocardial infarction (AMI), several preclinical studies have focused on influencing the inflammatory processes in the healing response post-AMI. The initial purpose of this healing response is to clear cell debris of the injured cardiac tissue and to eventually resolve inflammation and support scar tissue formation. This is a well-balanced reaction. However, excess inflammation can lead to infarct expansion, adverse ventricular remodeling and thereby propagate heart failure development. Different macrophage subtypes are centrally involved in both the promotion and resolution phase of inflammation. Modulation of macrophage subset polarization has been described to greatly affect the quality and outcome of healing after AMI. Therefore, it is of great interest to reveal the process of macrophage polarization to support the development of therapeutic targets. The current review summarizes (pre)clinical studies that demonstrate essential molecules involved in macrophage polarization that can be modulated and influence cardiac healing after AMI.

High-fat diet feeding affects osteoarthritis progression in a surgical mouse model with established and developing metabolic syndrome

High-fat diet feeding affects osteoarthritis progression in a surgical mouse model with established and developing metabolic syndrome

Therapeutic Tissue Regeneration by a Macrophage Colony-Stimulating Factor Fc Conjugate

Therapeutic Tissue Regeneration by a Macrophage Colony-Stimulating Factor Fc Conjugate

Assessment of phagocytic activity of cultured macrophages using fluorescence microscopy and flow cytometry.

Phagocytosis is the process by which phagocytes, including macrophages, neutrophils and monocytes, engulf and kill invading pathogens, remove foreign particles, and clear cell debris. Phagocytes and their ability to phagocytose are an important part of the innate immune system and are critical for homeostasis of the host. Impairment in phagocytosis has been associated with numerous diseases and disorders. Different cytokines have been shown to affect the phagocytic process. Cytokines including TNFα, IL-1β, GM-CSF, and TGF-β1 were found to promote phagocytosis, whereas high mobility group box-1 (HMGB1) inhibited the phagocytic function of macrophages. Here, we describe two commonly used methods to assess the phagocytic function of cultured macrophages, which can easily be applied to other phagocytes. Each method is based on the extent of engulfment of FITC-labeled latex minibeads by macrophages under different conditions. Phagocytic activity can be assessed either by counting individual cells using a fluorescence microscope or measuring fluorescence intensity using a flow cytometer.

Endometriosis, a disease of the macrophage

Endometriosis, a common cause of pelvic pain and female infertility, depends on the growth of vascularized endometrial tissue at ectopic sites. Endometrial fragments reach the peritoneal cavity during the fertile years: local cues decide whether they yield endometriotic lesions. Macrophages are recruited at sites of hypoxia and tissue stress, where they clear cell debris and heme-iron and generate pro-life and pro-angiogenesis signals. Macrophages are abundant in endometriotic lesions, where are recruited and undergo alternative activation. In rodents macrophages are required for lesions to establish and to grow; bone marrow-derived Tie-2 expressing macrophages specifically contribute to lesions neovasculature, possibly because they concur to the recruitment of circulating endothelial progenitors, and sustain their survival and the integrity of the vessel wall. Macrophages sense cues (hypoxia, cell death, iron overload) in the lesions and react delivering signals to restore the local homeostasis: their action represents a necessary, non-redundant step in the natural history of the disease. Endometriosis may be due to a misperception of macrophages about ectopic endometrial tissue. They perceive it as a wound, they activate programs leading to ectopic cell survival and tissue vascularization. Clearing this misperception is a critical area for the development of novel medical treatments of endometriosis, an urgent and unmet medical need.

Characterisation of microglia during de- and remyelination: Can they create a repair promoting environment?

Microglia play a key role in the initiation and perpetuation of de- and remyelination because of their ability to present antigens and clear cell debris by phagocytosis. Different factors expressed or secreted by microglia seem to play an important role in regenerative processes. But it remains unclear which factors lead to a protective microglial phenotype and recent data indicate region-specific differences within the central nervous system (CNS) for both de-/remyelination and microglial response. In order to identify important factors that promote neuroprotection, we examined changes in microglial phenotypes in the cuprizone model. We undertook an extensive and detailed analysis of the expression of surface markers as well as cytokines, growth factors, and the phagocytosis activity of microglia. We found a pronounced increase of phagocytosis activity of microglia during demyelination associated with an upregulation of phagocytic receptors, from which TREM-2b was the most prominent. The expression of MHC II was only increased at the peak of demyelination but costimulatory molecules showed no significant changes. Interestingly, the proinflammatory cytokine TNF-α was upregulated while the anti-inflammatory cytokines IL-10 and TGF-ß remained unchanged. The growth factors IFG-1 and FGF-2, which were both suggested to promote remyelination, were increased during demyelination. Our findings characterise changes of microglial markers during de- and remyelination indicating that debris clearance mediated via TREM-2b plays a central role in the regulation of these processes. Microglial phagocytosis as well as production of TNF-α, IGF-1, and FGF-2 seems to be important factors for the creation of an environment promoting regeneration.

The origin and differentiation of microglial cells during development

Some authors claim that microglia originate from the neuroepithelium, although most now believe that microglial cells are of mesodermal origin, and probably belong to the monocyte/macrophage cell line. These cells must enter the developing central nervous system (CNS) from the blood stream, the ventricular space or the meninges. Afterward microglial cells are distributed more or less homogeneously through the entire nervous parenchyma. Stereotyped patterns of migration have been recognized during development, in which long-distance tangential migration precedes radial migration of individual cells. Microglial cells moving through the nervous parenchyma are ameboid microglia, which apparently differentiate into ramified microglia after reaching their definitive location. This is supported by the presence of cells showing intermediate features between those of ameboid and ramified microglia. The factors that control the invasion of the nervous parenchyma, migration within the developing CNS and differentiation of microglial cells are not well known. These phenomena apparently depend on environmental factors such as soluble or cell-surface bound molecules and components of the extracellular matrix. Microglial cells within the developing CNS are involved in clearing cell debris and withdrawing misdirected or transitory axons, and presumably support cell survival and neurite growth.