Resident cells

Melanocortin peptides have been proposed as potent modulators of many pathologies including inflammatory (asthma, arthritis) and cardiovascular disease. They have been shown to be directed against resident cells within tissue such as macrophages, endothelial cells and also circulating leukocytes (neutrophils and lymphocytes). Therefore harnessing their therapeutic potential could lead to the development of novel therapeutics. 

Tissue resident cells derived from monocytes... 

Inflammation is a normal response to injury and, with persistent antigen or injury, results in the polarization of a profibrotic microenvironment where resident cells and inflammatory cells promote matrix deposition and not degradation. 

Fibrosis is a dynamic progression of dysregulated wound healing that results from chronic inflammation. It is a common pathology regardless of the tissue involved, and therefore, the mechanisms that progress to fibrosis can be widely applied. The recruitment, activation, and proliferation of inflammatory cells and their cooperation with resident cells appears to rely on the action of chemokines and the differential expression of the chemokine receptors by these cells. Thus, chemokine receptors make particularly attractive therapeutic targets. 

Pitzalis et al. have studied the influence and molecular alternation of retrorsine on rat hepatic cell cycle. Retrorsine has been found to block proliferation of resident cells. Cyclin D1 mRNA and protein levels were found to be elevated in rats treated with this alkaloid. The PCNA was also elevated . ... 

The conclusion from this study is that such a persistent block outside the resisting phase may contribute to selective replacement of resident cells during liver repopulation. 

Inflammation is part of the first line response of the immune system to infection. Inflammation is characterized by two main components an exudative response and a cellular response. The exudative response involves the local recruitment of fluid (edema, swelling), containing proteins such as fibrin and immunoglobulins. The cellular response involves the release of cytokines from resident cells such as fibroblasts and the invasion of white blood cells into the inflamed tissue. Leukocytes take on an important role in inflammation by clearing the site from bacteria and cellular debris. In chronic inflammation an increased extravasation of neutrophils, monocytes, activated T cells, and macrophages to the inflamed site will persist. 

Although the cellular and molecular mechanisms underlying fibrosis are not fully explained, it is assumed that an inflammatory reaction is the initiating factor in the early stage of fibrosis and that this inflammatory process continues during the fibrotic process [77, 105, 106], Kupffer and endothelial cells are considered to be the most important resident cells involved in the local production of inflammatory mediators [24, 28, 29, 76], Besides causing the activation of HSC, the inflammatory mediators induce the expression of adhesion molecules, such as ICAM-1 and VCAM on endothelial cells, that direct neutrophils and monocytes into the inflamed liver tissue [41-43], Expression of adhesion molecules is also shown for KC and stellate cells [42, 107], Furthermore, chemotactic compounds are released by endothelial and KC to attract immune competent cells... 

The CNS also contains resident cells that are responsible for the innate immune response. The main cell types responsible for this function are microglia and astrocytes. 

Various tissue constructs have been reassembled from isolated constituents, including resident cell types whose numbers have been amplified or modified in culture. A three-dimensional co-culture system for human skin keratinocytes layered upon a synthetic mesh infiltrated with dermal fibroblasts, when floated to allow contact of the uppermost keratinocytes with air, exhibits stratification and cornification remarkably similar to in vivo squamous epithelia. This reconstructed epithelial model has been recommended as an in vitro replacement for dermal corrosivity testing. It has been anticipated that this and a similar noncomified model will have application in dermal and ocular irritation testing, but thus far validation studies have yielded mixed results. Reconstructed tissues can also provide context for basic toxicological research on aberrant cellular interactions with cellular and acellular constituents, as illustrated by invasion of cancerous epithelial cells into underlying dermis of a skin equivalent model. 

Becher B, Bechmann 1, Greter M (2006) Antigen presentation in autoimmunity and CNS inflammation how T lymphocytes recognize the brain. J Mol Med 84 532-543 Becher B, Prat A, Antel JP (2000) Brain-immune connection Immune-regulatory properties of CNS-resident cells. GLIA 29 293-304... 

After binding and phagocytosis, alveolar macrophages and monocytes release pro-inflammatory cytokines, e.g. lL-1, interferon-y and tumor necrosis factor-a (fig. 1). These cytokines activate resident cells (epithelial cells, fibroblasts) to produce chemokines such as lL-8, granulocyte-monocyte-colony-stimulating factor, RANTES (regulated on activation normal T cell expressed and secreted) that will result in a second wave of cell recruitment (mononuclear and polymorphonuclear cells). 

Axel R (2005). Scents and sensibility A molecular logic of olfactory perception (Nobel lectui e). Angew Chem Int Ed Engl 44 6110-6127. Becher B, Prat A, An tel JP (2000). Brain-immune connection Immuno-regulatory properties of CNS-resident cells. Glia 29 293—304. 

Percupo CM, Hooks JJ, Sliinohai a T, Caspi R (1990) Detiick B Cytokine-mediated acdvadon of a neui onal rednal resident cell provokes andgen presentadon. J Immunol 145 4101 107. 

Becher B, Prat A, An tel JP (2000) Brain-immune counecdon Immuno-regulatory properdes of CNS-resident cells. Glia 29 293—304. 

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