Stromal inflammatory cells

FIGURE 14.11 Lymphoepithelioma-like gastric carcinoma. A, The large neoplastic cells have prominent nucleoli and blend in with the background inflammatory cells. B, An AEl /AE3 cytokeratin stain highlights the carcinoma cells. C, In this neoplasm, MLH-1 is lost in the tumor cell nuclei as compared with the intact (positive) staining of lymphocyte and stromal cell nuclei. D, In this example, the tumor cell nuclei are positive for Epstein-Barr virus mRNA (in situ hybridization) and the inflammatory and stromal cells are negative. 

The desmoplastic stroma associated with DAs expresses a variety of inflammatory and stromal markers. The inflammatory cells are mostly T cells (CD3 positive). Scattered B cells (CD20 positive) and macrophages (MAC387 and KPl positive) are also usually present. The spindle cells express alpha-smooth muscle actin, smooth muscle myosin heavy chain, and collagen IV, markers of myofibroblastic differentiation.They are also reported to be positive for heat shock protein 47 and hbronectin, as well as for proteins associated with tissue remolding such as urokinase-type plasminogen... 

Ajami K, Pitman MR, Wilson CH et al (2008) Stromal cell-derived factors lalpha and Ibeta, inflammatory protein-10 and interferon-inducible T cell chemo-attractant are novel substrates of dipeptidyl peptidase 8. FEBS Lett 582 819-825 Albright AV, Shieh JT, O Connor Ml et al (2000) Characterization of cultured microglia that can be infected by HIV-1. J Neurovirol 6(Suppl 1) S53-S60 Allen SJ, Crown SE, Handel TM (2007) Chemokine receptor structure, interactions, and antagonism. Annu Rev Immunol 25 787-820... 

De Klerck B, Geboes L, Hatse S, et al. Pro-inflammatory properties of stromal cell-derived factor-1 (CXCL12) in collagen-induced arthritis. Arthritis Res Ther 2005 7(6) R1208-1220. 

Consistent with their role as immune receptors, each human TLR is expressed by at least one subset of myeloid cells (MCs) or lymphocytes [7,8]. TLRs are also present on stromal elements like endothelium particularly after local inflammatory stimulus [9-11]. These distribution patterns can determine the physiological consequences of stimulation or antagonism, and affect the balance of toxicity versus therapeutic effect. Another consideration for medicinal chemistry is subcellular localization of TLRs. While most are expressed on the cell surface, some (TLRs 3,7,8, and 9) can localize to endosomes where they survey ingested material for ligands, so drug access to this compartment can be crucial when targeting these TLRs [12]. 

Silk fibers or monolayers of silk proteins have a number of potential biomedical applications. Biocompatibility tests have been carried out with scaffolds of fibers or solubilized silk proteins from the silkworm Bombyx mori (for review see Ref. [38]). Some biocompatibility problems have been reported, but this was probably due to contamination with residual sericin. More recent studies with well-defined silkworm silk fibers and films suggest that the core fibroin fibers show in vivo and in vivo biocompatibility that is comparable to other biomaterials, such as polyactic acid and collagen. Altmann et al. [39] showed that a silk-fiber matrix obtained from properly processed natural silkworm fibers is a suitable material for the attachment, expansion and differentiation of adult human progenitor bone marrow stromal cells. Also, the direct inflammatory potential of silkworm silk was studied using an in vitro system [40]. The authors claimed that their silk fibers were mostly immunologically inert in short and long term culture with murine macrophage cells. 

Tumor necrosis factor a (TNF-a) is a multifunctional cytokine produced by activated monocytes-macrophages. TNF-a is one of the most potent osteoclastogenic cytokines produced in inflammation, and, in addition, TNF-a induces IL-1 synthesis. Like the other known stimulators of bone resorption, it acts through osteoblastic cells however, it has been demonstrated that TNF-a is able to induce osteoclast formation from stromal-depleted macrophages, with potency similar to that of RANKL (Kobayashi et al. 2000). TNF-a is able to induce bone resorption in vitro (Thomson et al. 1987) as well as in vivo (Koning et al. 1988). Osteoclasts induced by TNF-a have the capacity to form resorption pits on dentine slices only in the presence of IL-la. TNF-a, together with IL-1, plays an important role in bone resorption in inflammatory diseases (Kobayashi et al. 2000). Inhibition of TNF by TNF binding protein (TNFbp) completely prevents bone loss and osteoclast formation (Kimble et al. 1997). 

Keratinocytes secrete a unique profile of chemo-kines and cytokines after exposure to proinflam-matory cytokines. Keratinocyte-derived thymic stromal lymphopoietin (TSLP) may be of particular importance in atopic dermatitis This protein is undetectable in normal skin or non-lesional skin in patients with atopic dermatitis, but is highly expressed in acute and chronic atopic dermatitis lesions [18]. TSLP instructs human dendritic cells to create a Th-2-permissive microenvironment by inducing the expression of OX40L which triggers the differentiation of inflammatory Th-2 cells [48]. 

Corneal edema is a common finding postoperatively after uncomplicated, sutureless, scleral tunnel or clear corneal incision cataract surgery. More severe involvement (Figure 30-5) with persistent stromal edema, epithelial microcysts, and bullae may be found in patients with low endothelial cell counts, excessive inflammation from corneal trauma during the surgery, or an increased lOP secondary to retained lens material or inflammatory response. Bullae are typically secondary to increased corneal aqueous absorption due to high lOP or to a breakdown of the corneal endothelial aqueous pump. 

---