RESUMO
Malaria and human immunodeficiency virus (HIV) coinfections are common in pregnant women in sub-Saharan Africa. The current study shows that placentas of malaria-infected women contain 3 times as much CC chemokine receptor 5 (CCR5) RNA as placentas of women without malaria. By immunohistochemistry, CCR5(+) maternal macrophages were seen in placentas from malaria-infected women but not in placentas from malaria-uninfected women. In addition, CCR5 also was found on fetal Hofbauer cells in placentas from both groups. Thus, malaria infections increase the potential reservoir for HIV in the placenta by increasing the number of HIV target cells.
Assuntos
Infecções por HIV/transmissão , Macrófagos/metabolismo , Malária/imunologia , Placenta/imunologia , Complicações Parasitárias na Gravidez/imunologia , Receptores CCR5/genética , Antígenos CD4/biossíntese , Antígenos CD4/genética , Feminino , Feto/imunologia , Técnica Direta de Fluorescência para Anticorpo , Humanos , Imuno-Histoquímica , Receptores de Lipopolissacarídeos/biossíntese , Receptores de Lipopolissacarídeos/genética , Gravidez , RNA Mensageiro/biossíntese , Receptores CCR5/biossíntese , Receptores CCR5/imunologia , Receptores de Quimiocinas/biossíntese , Receptores de Quimiocinas/genética , Ativação TranscricionalRESUMO
13-S-Hydroxyoctadecadienoic acid (13-S-HODE), the product of 15-lipoxygenase (15-LOX) metabolism of linoleic acid, enhances cellular mitogenic responses to certain growth factors. Other observations have questioned whether 13-S-HODE has tumorigenic effects. Our study evaluated the hypothesis that 15-LOX-1 is overexpressed in colon cancers resulting in an increase in intracellular 13-S-HODE. 15-LOX-1 and 13-S-HODE were quantified using western blots, ELISA and immunohistochemistry in 18 human colon cancers with paired normal colonic mucosa. Additionally, 15-LOX-1 expression was measured by western blots in three transformed colonic cell lines and in a human umbilical vein endothelial cell line. Next, we evaluated 13-S-HODE effects on cellular proliferation, cell cycle distribution and apoptosis in a transformed colonic cell line (RKO). Cell cycle distributions were measured by flow cytometry and apoptosis was assessed by phase contrast microscopy, electron microscopy, flow cytometry and DNA fragmentation assay. 15-LOX-1 immunohistochemistry staining scores were reduced in tumor tissues (P
Assuntos
Araquidonato 15-Lipoxigenase/metabolismo , Neoplasias do Colo/metabolismo , Ácidos Linoleicos/metabolismo , Apoptose , Western Blotting , Ciclo Celular , Divisão Celular , Neoplasias do Colo/enzimologia , Neoplasias do Colo/patologia , Ensaio de Imunoadsorção Enzimática , Humanos , Imuno-Histoquímica , Células Tumorais CultivadasRESUMO
Altered cellular immunity in patients with advanced head and neck cancer includes impairments in lymphokine production, blastogenesis, in vitro cytotoxicity, and T-cell levels. Recent evidence for the potential importance of in lymphokine interleukin 2 (IL-2) in patients with cancer prompted a study of the kinetics of IL-2 receptor expression on lymphocytes from patients with untreated advanced head and neck cancer and normal subjects and an evaluation of the in vitro effects of the T-cell immune-reconstituting peptide, thymosin alpha 1. Concanavalin A-stimulated IL-2 receptor expression was maximal after 72 hours and was higher in normal subjects than in patients. This was due to lower levels of helper/inducer (CD4) cells expressing IL-2 receptors in the patients compared with the normal subjects. Thymosin alpha 1 further decreased levels of IL-2 receptor-positive (both CD4 and CD8) cells at 48 and at 72 hours. At 96 hours, levels of IL-2 receptor-positive cells and proportions of cells in G2 and M phases of the cell cycle were similar among both groups of subjects. Simultaneous cell kinetic studies indicated that thymosin alpha 1 down regulation of IL-2 receptors was not due to an effect on proliferation and that differences in IL-2 receptor expression at 72 hours among normal subjects and the patients with cancer were more likely related to differences in cell proliferation kinetics.
Assuntos
Carcinoma de Células Escamosas/imunologia , Neoplasias de Cabeça e Pescoço/imunologia , Receptores de Interleucina-2/metabolismo , Antígenos CD4/análise , Concanavalina A/farmacologia , Regulação para Baixo/efeitos dos fármacos , Citometria de Fluxo , Humanos , Cinética , Receptores de Interleucina-2/efeitos dos fármacos , Timosina/farmacologiaRESUMO
Impaired cell-mediated immunity has been consistently demonstrated in patients with advanced head and neck squamous cancer (HNSC); however, the results of prior studies of correlations of cellular immune parameters with treatment outcome have been inconsistent, and routine assessment of immune parameters has been of limited clinical use. To determine the prognostic importance of alterations in the proportions of various T-lymphocyte subpopulations in the peripheral blood of patients with HNSC, levels of T3, T4, T6, T8, T9, T10, T11, and Leu 7 cells were quantitated by flow cytometry in 80 previously untreated patients and prospectively correlated with tumor characteristics and clinical course (median length of follow-up, 27 months). The mean helper/suppressor cell ratio (T4/T8) increased progressively with increasing tumor stage and was significantly elevated among patients with cancer as a group and in patients with advanced (stage III or IV) disease compared with 40 normal subjects. Decreased disease-free survival was significantly associated with elevated T4/T8 ratios and low percent T8 and T11 cell levels. The prognostic significance of percent T8 (cytotoxic/suppressor) cell levels persisted even after adjusting for known prognostic factors of tumor stage, T class, N class, and tumor site. These correlations provide new insight into immune alterations in HNSC that may prove useful in identifying patients with early clinical disease who have a poor prognosis.
