Fibroblasts, resident

Fig. 14.1. The Thl/Th2 balance is central to the regulation of normal wound repair. Tissue injury results in the initiation of an inflammatory response, mediated by a variety of cells and their by-products. Immune cells are recruited and cross-regulate the Thl/ Th2 balance that occurs in response to the cytokine environment. This balance is in turn cross-regulated by the chemokine/chemokine-receptor expression profile, which functions to amplify the inflammatory process. Cells residing in the injured tissue release profibrotic mediators, which promote fibroblast activation, proliferation, and differentiation to the myofibroblast phenotype. Myofibroblasts produce collagen to repair damaged tissue, which is an event that is favored by the inhibition of MMP activity. The Thl/Th2 balance is central to whether a normal or aberrant wound-repair process is established A Thl environment promotes normal tissue resolution (fibrinolysis), whereas a Th2 environment maintains the progression of fibrotic disease (excessive collagen deposition).

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...

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. 

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. 

Oxidised LDL is toxic toward endothelial cells, smooth muscle cells and fibroblasts [18]. The toxic principle has not yet been identified, but it is proven that the protein moiety is not required. The toxic components reside in the lipid phase of Ox-LDL. In cultured fibroblasts and endothelial cells, the cytotoxicity and inhibition of growth essentially reside in 2,4-alkadienals (nonadienal, decadienal) and 4-hydroxynonenal, which produce 50% inhibition of endothelial cell proliferation. Lysophosphatides are present in Ox-LDL and have been shown to produce deleterious effects in cells, such as inhibition of the Na/K pump [18]. It has been suggested that oxidation of LDL results in an activation of a previously masked phospholipase A2 activity of apoB [21], which results in the release of lysophosphatides and oxidised fatty acids. Lysophosphatides act as chemoattractants for blood monocytes [22],... 

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). 

Sawker et al. reported that IV-nonyl-DNJ (97) is a potent inhibitor of lysosomal /3-glucosidase, with an IC50 value of 1 pM, and the addition of subinhibitory concentration (10 pM) of this compound to a fibroblast culture medium leads to a 2-fold increase in the mutant (N370S) enzyme activity [135]. Very recently, examination of a series of DNJ analogues on the resid-... 

Postlethwaite, A.E. and Seyer, J.M. (1991). Fibroblast chemotaxis induction by human recombinant interleukin-4. Identification by synthetic peptide analysis of two chemotactic domains residing in amino acid sequences 70-88 and 89-122. 

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