Diversity and plasticity are hallmarks of cells of the monocyte-macrophage lineage. In response to IFNs, Toll-like receptor engagement, or IL-4/IL-13 signaling, macrophages undergo M1 (classical) or M2 (alternative) activation, which represent extremes of a continuum in a universe of activation states. Progress has now been made in defining the signaling pathways, transcriptional networks, and epigenetic mechanisms underlying M1-M2 or M2-like polarized activation. Functional skewing of mononuclear phagocytes occurs in vivo under physiological conditions (e.g., ontogenesis and pregnancy) and in pathology (allergic and chronic inflammation, tissue repair, infection, and cancer). However, in selected preclinical and clinical conditions, coexistence of cells in different activation states and unique or mixed phenotypes have been observed, a reflection of dynamic changes and complex tissue-derived signals. The identification of mechanisms and molecules associated with macrophage plasticity and polarized activation provides a basis for macrophage-centered diagnostic and therapeutic strategies.

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Macrophage plasticity and polarization: in vivo veritas

Macrophage Diversity Enhances Tumor Progression and Metastasis

Evidence from clinical and experimental studies indicates that macrophages promote solid-tumour progression and metastasis. Macrophages are educated by the tumour microenvironment, so that they adopt a trophic role that facilitates angiogenesis, matrix breakdown and tumour-cell motility — all of which are elements of the metastatic process. During an inflammatory response, macrophages also produce many compounds — ranging from mutagenic oxygen and nitrogen radicals to angiogenic factors — that can contribute to cancer initiation and promotion. Macrophages therefore represent an important drug target for cancer prevention and cure.

Tumour-educated macrophages promote tumour progression and metastasis

Tumor-associated macrophages: from mechanisms to therapy.

Macrophages are prominent in the stromal compartment of virtually all types of malignancy. These highly versatile cells respond to the presence of stimuli in different parts of tumors with the release of a distinct repertoire of growth factors, cytokines, chemokines, and enzymes that regulate tumor growth, angiogenesis, invasion, and/or metastasis. The distinct microenvironments where tumor-associated macrophages (TAM) act include areas of invasion where TAMs promote cancer cell motility, stromal and perivascular areas where TAMs promote metastasis, and avascular and perinecrotic areas where hypoxic TAMs stimulate angiogenesis. This review will discuss the evidence for differential regulation of TAMs in these microenvironments and provide an overview of current attempts to target or use TAMs for therapeutic purposes. (Cancer Res 2006; 66(2): 605-12)

https://cancerres.aacrjournals.org/content/canres/66/2/605.full.pdf

Distinct Role of Macrophages in Different Tumor Microenvironments

In the leg venous valves isolate the blood into short columns and thus relieve the vessel wall from the gravitational force of blood columns that would otherwise be several feet in length. Class 6 chronic venous insufficiency is associated with abnormal venous hemodynamics and associated tissue-related abnormalities termed lipodermatosclerosis, accompanied by ulceration. Ingenious surgical techniques have focused on correction of the abnormal hemodynamics by repair, reconstruction, or transplantation of venous valves to the deep venous system of the lower extremity with varying success rates. We have applied free scapular fasciocutaneous flaps to successfully reconstruct recalcitrant grade 6 venous insufficiency ulcers in the lower extremity. We have noticed such ulcers frequently in medial malleolar, lateral malleolar or dorsum pedis but never in the region of the gastrocnemius or peroneus muscles. This fact prompted us to examine the microvenous valvular anatomy in segments of human leg.

Microvenous Valvular Mapping in the Human Lower Extremity. Valvular Density Alone Cannot Account for Sites of Chronic Venous Stasis and Ulceration.

A departmental history is mirrored by its members and their scientific and clinical output. In honour of Prof. Ernst Wolners retirement the authors were invited to summarize various aspects of basic and applied research performed at the Department of Cardiothoracic Surgery in Vienna within the last decade. This free communications suffices to present a short introduction of work performed by four independent laboratories headed by staff surgeons.

Basic and applied research at the department of cardio-thoracic surgery : work in progress

Persistent plasminogen activator inhibitor 1 gene expression in cardiac transplant recipients with idiopathic dilated cardiomyopathy.

incubated at 37°C for 4 h. Cell morphology and viability were examined and the cytokine profile in the culture medium was determined. Results: Cell morphology changed during CIT as cell-to-cell contact was reduced, suggesting cytoskeletal rearrangements. When cells underwent 6 h CIT, the morphology recovered after reperfusion without significant cell death. Of 42 cytokines examined, 16 were significantly increased in culture medium, including IL-8, IL-6, IFN , MCP-3, IL-12(p70), IL-7, GRO, TNF , TNF , VEGF and G-CSF. When CIT was prolonged to 18 h, many cells were detached from the culture plates with reduced viability. Cell death switched from apoptosis to necrosis after reperfusion, as determined by flow cytometry. Conclusions: The simulated IR-injury model has important features of actual lung transplantation. Inflammatory responses and cell death induced by hypothermic IR in human lung epithelial cells are similar to those seen in animal and clinical studies. This model system could be used to further determine the molecular mechanisms and to develop effective therapies for IR-induced inflammation and cell death.

Seyedhossein Aharinejad

Papers

Microvenous Valvular Mapping in the Human Lower Extremity. Valvular Density Alone Cannot Account for Sites of Chronic Venous Stasis and Ulceration.

Basic and applied research at the department of cardio-thoracic surgery : work in progress

Persistent plasminogen activator inhibitor 1 gene expression in cardiac transplant recipients with idiopathic dilated cardiomyopathy.

628 A Single-Dose Recombinant Glutathione s-Transferase P1-1 Improves Cardiac Function Post Myocardial Infarction in Rats

Suppression of the Apoptosis Inhibitor Apollon Programmed Cell Death in Idiopathic Dilated Cardiomyopathy is Mediated by