Fibroblast constituents

Double stranded (ds) RNA is not a constituent of a normal cells but is produced during replication of many RNA and DNA viruses either as an obligatory intermediate or as a side product. As a foreign molecule, double stranded RNA induce the secretion of interferon (EFN) from lymphocytes, neutrophils and fibroblasts. 

Particle deposition in the respiratory tract can initiate inflammatory responses. With repeated deposition, inflammation becomes chronic, and the site or sites of deposition beeome laden, not only with the particulates, but with several types of cells—fibroblasts, macrophages, leukocytes, and lymphocytes. These cells are normal constituents of the lung, an organ composed predominantly of connective tissue. Lung connective tissue forms the thin membrane that defines the functional alveolar-capillary unit. Inside this air sac and on the membrane are specialized eells required for gas exchange, maintenance, and repair (Fig. 3.6). 

Fig. 6.10. In vivo multiplex CARS microspectroscopy of a NIH 3T3-L1 fibroblast cell in the high-wavenumber region where C-H stretch vibrations reside. A CARS image revealing the intracellular distribution of constituents with high densities of lipids, such as the membrane envelope of the nucleus and intracellular lipid droplet (LD) organelles. Typical MEM-reconstructed Raman spectra taken for (B) a single LD organelle that is indicated by the arrow in A, (C) the nucleus, and (D) the cytoplasm. The spectrum exposure time was 0.3 s...

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. 

LDL is oxidatively modified when incubated in vitro with three major cellular constituents of the vascular wall endothelial cells [35], vascular smooth muscle cells [35] and macrophages [35-37], The uptake of oxidised LDL occurs via the scavenger-receptor pathway, and expression of scavenger receptors has been demonstrated on macrophages, endothelial cells [38], fibroblasts [39] and smooth muscle cells [39]. Unlike the LDL receptor, expression of the scavenger receptor is not down-regulated by an increase in intracellular cholesterol [40]. Therefore, uptake of Ox-LDL contributes to the accumulation of cholesteryl esters in foam cells of atherosclerotic lesions [40]. Now, the question is Does oxidation of LDL-lipids influence the development of atherosclerosis ... 

The disruption of the capillary wall allows movement of macrophages and other plasma constituents into Bowman s space and stimulates the formation of crescents, which are composed mainly of parietal epithelial cells, as well as macrophages and fibroblasts. Crescent formation indicates the severity of the glomerular capillary disease but not its pathogenesis. The age of crescents can serve as a marker for disease duration and the likelihood of successful therapeutic intervention. ... 

Fig. 5. Cyclic changes in cholesterol metabolism that occur in cultured human fibroblasts when LDL is removed from the culture medium (-LDL) and is subsequently returned to the medium (+LDL). The relative level of each constituent is indicated by the size of the square. Reproduced, with permission of the authors and publishers, from Goldstein and Brown [10].

The first indication that Ras functions downstream from RTKs in a common signaling pathway came from experiments in which cultured fibroblast cells were induced to proliferate by treatment with a mixture of PDGF and EGF. Microinjection of anti-Ras antibodies into these cells blocked cell proliferation. Conversely, injection of Ras , a constitu-tively active mutant Ras protein that hydrolyzes GTP very inefficiently and thus persists in the active state, caused the cells to proliferate in the absence of the growth factors. These findings are consistent with studies showing that addition of FGF to fibroblasts leads to a rapid increase in the proportion of Ras present in the GTP-bound active form. 

It is now many years since it was discovered that heparin is a constituent of the mast cell granule. Because it has been found in mast cells, many assume that this cell is the principal site of synthesis of this polysaccharide. However, there is evidence also that fibroblasts not only make hyaluronic acid, but possibly sulfated chondroitin polysaccharides as well. - There is not always a distinct correlation between the numbers of mast cells and the content of heparin of a particular tissue. The mast cell is found only in connective and reticular tissues. There is some evidence that mast cells in culture may synthesize heparin.However, another point of view has been put forward that the fibroblasts may make the polysaccharide and store it for a time and that, when they are full of these storage granules, they are called mast cells. ... 

Cemilton , a product obtained from rye pollen, is an effective agent in the treatment of prostatic inflammatory disease and benign prostatic hyperplasia [139]. In 1995, DIBOA was identified as a constituent of the water soluble pollen extract [66]. The purified active fraction of Cemilton showed dose-dependent effects on DNA-synthesis in epithelial cells. At low concentrations, DNA synthesis was stimulated, indicated by a 300% increase in radiolabelled thymidine incorporation. Concentrations larger than 1 pg/ml resulted in an inhibition up to 80% after 5 days of exposure. Fibroblast cells react in a similar way and prostate DU 145 cells showed the same inhibition after treatment with the active fraction as they do after exposure to synthetic DIBOA. From the studies is was clear, that DIBOA must be causative for the effects of Cemilton. Cell growth inhibition was thought to be due to the chelating properties of the compound [67]. As demonstrated MCF-7 breast cancer-and COS-7-cells were inhibited as well [140]. From the morphology of treated DU-145 cells the authors concluded DIBOA-induced cell death. 

The pathogenesis of pulmonary fibrosis is presumably related to initial loss of alveolar type I epithelial cells and endothelial cells. However, the dysregulated repair of pulmonary fibrosis is followed by persistence of inflammation. This is followed by proliferation of type II cells, recruitment and proliferation of endothelial cells and fibroblasts, and deposition of extracellular matrix leading to end-stage alveolar and interstitial fibrosis. These events involve the complex and dynamic interplay between diverse immune effector cells and cellular constituents of the alveolar-capillary membrane and interstitium of the lung. Interaction of these diverse cell populations and the cytokines that they produce culminate in chronic inflammation, angiogenesis, fibroproliferation, and deposition of extracellular matrix. 

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