Leishmania spp. are intracellular parasites that cause lesions in the skin, mucosa, and viscera. We have previously shown that Leishmania infection reduces mononuclear phagocyte adhesion to inflamed connective tissue. In this study, we examined the role of adhesion molecules and chemokines in this process. Infection rate (r ؍ ؊0.826, P ؍ 0.003) and parasite burden (r ؍ ؊0.917, P ؍ 0.028) negatively correlated to mouse phagocyte adhesion. The decrease (58.7 to 75.0% inhibition, P ؍ 0.005) in phagocyte adhesion to connective tissue, induced by Leishmania, occurred as early as 2 h after infection and was maintained for at least 24 h. Interestingly, impairment of cell adhesion was sustained by phagocyte infection, since it was not observed following phagocytosis of killed parasites (cell adhesion varied from 15.2% below to 24.0% above control levels, P > 0.05). In addition, Leishmania infection diminished cell adhesion to fibronectin (54.1 to 96.2%, P < 0.01), collagen (15.7 to 83.7%, P < 0.05), and laminin (59.1 to 82.2%, P < 0.05). The CD11b hi subpopulation was highly infected (49.6 to 97.3%). Calcium and Mg 2؉ replacement by Mn 2؉ , a treatment that is known to induce integrins to a high state of affinity for their receptors, reverted the inhibition in adhesion caused by Leishmania. This reversion was completely blocked by anti-VLA4 antibodies. Furthermore, expression of CCR4 and CCR5, two chemokine receptors implicated in cell adhesion, was found to be downregulated 16 h after infection (2.8 to 4.1 times and 1.9 to 2.8 times, respectively). Together, these results suggest that mechanisms regulating integrin function are implicated in the change of macrophage adhesion in leishmaniasis.
In this work, we have developed an adhesion assay to study interactions between mononuclear phagocytes and connective tissue in vitro and show its potential use to study diseases caused by intracellular microorganisms. The assay reproduces most of the characteristics of macrophage adhesion to connective tissue in vivo, such as: preferential adhesion to inflamed connective tissue, divalent cation and integrin dependence, and up-regulation upon cell activation. The phagocyte adhesion to connective tissue was inhibited by infection with Leishmania (58+/-22%, p < 0.05) and was not affected by infection with Mycobacterium or by endocytosis of latex beads. Manganese partially reverted the loss in adherence produced by Leishmania infection, indicating that the mechanisms regulating the function of integrins are affected by cell infection with Leishmania. This assay might be a useful tool for the study of the mechanisms by which mononuclear phagocytes play a role in the immune-inflammatory response and in the development of lesions.
Abstract. The inhibitors of apoptosis proteins (IAPs) act by directly blocking cleaved caspase-3 (XIAP) or the protein SMAC/DIABLO, an antagonist. The inhibition of XIAP activity or the increase of SMAC activity might improve the therapeutic response of the patients. This work evaluated the immunoexpression of IAPs and SMAC in colorectal carcinoma and their correlation with apoptotic index (AI), cellular proliferation, p53 protein immunoexpression and patient survival rate. TMA paraffin blocks were made with colorectal cancer tissue and adjacent non-tumorous mucosa of 130 patients, not submitted to radio or chemotherapy. Sections of 4 μm were processed by immunohistochemistry for survivin, XIAP, cIAP-1, cIAP-2 and SMAC, and the immunoexpression scores were obtained. They were correlated between each other and with the AI obtained by anticleaved caspase-3 and M30 (cleaved cytokeratin-18) antibodies, the cellular proliferation index, p53 protein immunoexpression and patient survival data. Direct correlation occurred between the four IAPs studied in tumor and nontumorous mucosa tissues. SMAC, survivin, cIAP-1 and cIAP-2 were positively correlated with tumoral tissue AI. Cellular proliferation and p53 immunoexpression was positively correlated with XIAP, SMAC and cIAP-1 scores. Low cIAP-1 immunoexpression showed a tendency for correlation with shorter patient survival. Equilibrium between the activities of IAPs and SMAC was demonstrated by the direct correlation between their immunoexpression. Correlation between SMAC and AI confirmed the pro-apoptotic activity of this protein. XIAP showed no inverse correlation with AI. XIAP, SMAC and cIAP-1 play a role in colorectal tumorigenesis, as demonstrated by their direct correlation with cellular proliferation and p53 protein. The tendency for correlation between low cIAP-1 immunoexpression and survival might indicate a role for this protein as a prognostic marker in colorectal cancer.
Primary mucinous cystic neoplasms are extraordinarily rare tumors of the kidney. Herein, we present a case of a 52-year-old man who presented with painless hematuria and mucusuria. The nephrectomy showed a markedly enlarged kidney replaced by a large cystic mass filled with mucin and with almost complete destruction of the renal parenchyma. Histologically, the mass was lined primarily by simple mucinous epithelium and showed foci of adenomatous (borderline) change with focal areas exhibiting intraepithelial carcinoma. No invasion was documented after extensive sampling of the tumor. A pathologic diagnosis of intraepithelial carcinoma arising in a mucinous neoplasm of borderline malignancy was rendered. One year later, the patient presented with pseudomyxoma peritonei. This case illustrates that, in a patient with pseudomyxoma peritonei, the absence of an appendiceal, gastrointestinal, or ovarian primary tumor raises the possibility of a primary neoplasm at an unusual site such as the kidney.
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