Histology and histopathology Vol.17, nº 3 (2002)
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- PublicationOpen AccessCD44: functional relevance to inflammation and malignancy(Murcia : F. Hernández, 2002) Yasuda, M.; Nakano, K.; Yasumoto, K.; Tanaka, Y.CD44 is a principal cell surface receptor for hyaluronan, a major component of extracellular matrices. Cells are surrounded by and encounter matrix in vivo, which in turn serves a variety of cell functions through the direct adhesion via their receptors. CD44 communicates cell-matrix interactions into the cell via “outside-in signaling” and has an important role in biological activities. The interaction of CD44 with fragmented hyaluronan on rheumatoid synovial cells induces expression of VCAM-1 and Fas on the cells, which leads to Fas-mediated apoptosis of synovial cells by the interaction of T cells bearing FasL. On the other hand, engagement of CD44 on tumor cells derived from lung cancer reduces Fas expression and Fas-mediated apoptosis, resulting in less susceptibility of the cells to CTL-mediated cytotoxicity through Fas-FasL pathway. Thus, although the CD44-mediated signaling differs among cells and circumstances, we here propose the functional role of CD44 in inflammatory processes and tumor susceptibility and the rational design of future therapeutic strategies including the exploitation of CD44-mediated pathway in vivo.
- PublicationOpen AccessInflammatory cells induce neointimal growth in a rat arterial autograft model(Murcia : F. Hernández, 2002) Jurado, F.; Bellón, J.M.; Rodríguez, M.; Corrales, C.; Buján, J.Subendothelial invasion by leukocytes is a sign of intimal thickening in arteriosclerosis and in the response of a vessel to mechanical damage. Our study was designed to establish whether these cells are implicated in the formation of a neointima in an autologous arterial graft model in the rat and to evaluate the effects of cyclosporin A (CsA). Three study groups were established according to whether the animals were treated with CsA-Cp (Sandimmun)®, CsA-Et (ethanol vehicle) or received no treatment (control group). Both drug forms were administered (5 mg/kg/day, s.c.) from 4 days prior to surgery until the time of sacrifice. Antibodies specific for lymphocytes (CD4, CD8), monocytes/macrophages-ED1, smooth muscle a-actin and the von Willebrand factor (vWF) were used to identify the cells in the grafted arterial wall. In control grafts, the neointima had formed by 2 weeks postimplant. However, the cells comprising this layer generally presented no positivity whatsoever towards the antibodies employed. At 50 days, the new layer was observed to be formed by a vWF-positive endothelium and a-actin-positive cells. In all three groups, several polymorphonuclear (PMN) cells adhered to the denuded luminal surface from 7 days onwards. In the treated animals, neutrophils and monocytes were seen to infiltrate intimal and medial layers during the later postimplant stages. Around the third week post-implant, the neointima had reached the grafted segment from the distal portion of the recipient artery, and by 50 days it was similar to that seen in control specimens. Our findings suggest that: a) neutrophils play a role in neointimal thickening in this arterial autograft model; and b) CsA promotes the adhesion and infiltration of neutrophils in the injured arterial wall.
- PublicationOpen AccessThe role of the angiogenic molecule VEGF in the pathogenesis of rheumatoid arthritis(Murcia : F. Hernández, 2002) Afuwape, A.O.; Kiriakidis, S.; Paleolog, E.M.The expansion of the synovial lining of joints in rheumatoid arthritis (RA), and the subsequent invasion by the pannus of underlying cartilage and bone, necessitates an increase in the vascular supply to the synovium, to cope with the increased requirement for oxygen and nutrients. New blood vessel formation - ‘angiogenesis’ - is now recognised as a key event in the formation and maintenance of the pannus in RA. Although many pro-angiogenic factors have been demonstrated to be expressed in RA synovium, the potent pro-angiogenic cytokine vascular endothelial growth factor (VEGF) has been demonstrated to have a central involvement in the angiogenic process in RA. The additional activity of VEGF as a vascular permeability factor may also increase oedema and hence joint swelling in RA. Several studies, including those from the Kennedy Institute of Rheumatology Division, have shown that targeting angiogenesis in animal models of arthritis ameliorates disease. Inhibition of angiogenesis, as an adjunct to existing therapy of RA, or even as a stand-alone treatment, would not only prevent delivery of nutrients to the synovium, but could also lead to vessel regression and possibly reversal of disease.
- PublicationOpen AccessAntiproliferative effect of topic hyaluronic acid gel. Study in gingival biopsies of patients with periodontal disease(Murcia : F. Hernández, 2002) Mesa, F.L.; Aneiros, J.; Cabrera, A.; Bravo, M.; Caballero, T.; Revelles, F.; Del Moral, R.G.; O’Valle, F.Hyaluronic acid (HA) is the most abundant glycosaminoglycan of high molecular weight in the extracellular matrix of soft periodontal tissues. Our group recently demonstrated an HA-induced reduction in lymphoplasmocyte inflammatory infiltrate in periodontal disease. The objective of this study was to determine the effect of an HA gel of high molecular weight on cell proliferation, inflammation, and different periodontal lesion parameters. A double-blind clinical trial was conducted on the effect of an HA gel on cell proliferation in gingival biopsies from 28 patients with periodontal disease. A split-mouth design was used, randomly applying the gel to one quadrant and a placebo to the contralateral one. A gingival biopsy was taken for histopathological and immunohistochemical study, in order to determine the expression of cell proliferation antigen Ki-67 and to evaluate the inflammatory infiltrate. HA gel treatment induced a significant reduction in the proliferation index of the gingival epithelium, with 276 (range 234-317) Ki-67-positive cells per mm2 in treated samples versus 514 (range 158-876) per mm2 in controls (Mann-Whitney U test, p<0.003). In 13 patients, the number of Ki-67-positive fibroblastic cells was reduced by the treatment, whereas in 6 patients no differences were found (global difference, p=0.12). In 10 patients, Ki-67-positive cells were decreased in chronic inflammatory infiltrate present in the lamina propria, whereas in 6 patients no differences were found (global difference, p=0.054). We conclude that high molecular-weight HA gel reduces cell proliferation in epithelial cells such as fibroblasts and lymphocytes, abates the inflammatory process, and improves the periodontal lesion in patients with chronic periodontitis.
- PublicationOpen AccessPromotion of metastasis in nasopharyngeal carcinoma by Epstein-Barr virus latent membrane protein-1(Murcia : F. Hernández, 2002) Yoshizaki, T.Nasopharyngeal carcinoma (NPC) is a malignant tumor associated with Epstein-Barr virus (EBV). Latent membrane protein-1 (LMP-1) is an EBVencoded oncoprotein and is detected in approximately 50-70% of patients with NPC. LMP-1 is thought to play an essential role in tumorigenesis of NPC. In addition to its transforming properties, LMP-1 has been suggested to be associated with promotion of metastasis. Metastasis is a phenomenon composed of multiple sequential cascades. Reduction of tumor cell adhesion, degradation of extracellular matrix, basement membrane, enhancement of cell motility, and promotion of neovascularization are thought to be essential steps. LMP-1 down-regulates expression of E-cadherin, induces matrix metalloproteinase-9 and urokinase typeplasminogen activator through activation of NF-?B and AP-1, and enhances cell motility via ets-1 activation. LMP-1 also induces vascular endothelial growth factor through cyclooxygenase-2 activation and interleukin-8 through NF-?B activation. Clinical studies suggested the association of these factors with metastatic status of patients with NPC. In this review, the role of LMP-1 in the metastasis of NPC is discussed.