RESUMO
The determinants of the prevalence of CD8(+) T cells in the inflamed myocardium of Trypanosoma cruzi-infected patients and experimental animals are undefined. Using C3H/He mice infected with the Colombiana strain of T. cruzi, we found that the distribution of CD4(+)/CD8(-) and CD4(-)/CD8(+) T cells in the myocardium mirrors the frequency of cells expressing the CD62L(Low)LFA-1(High)VLA-4(High) activation phenotype among CD4(+)/CD8(-) and CD4(-)/CD8(+ )peripheral blood T cells. Consistently, vascular cell adhesion molecule-1-positive endothelial cells and a fine fibronectin network surrounding VLA-4(+) mononuclear cells were found in the inflamed myocardium. Further, interferon gamma (IFN-gamma) and IFN-gamma-induced chemokines (RANTES, MIG and CRG-2/IP-10), as well as JE/MCP-1 and MIP1-alpha, were found to be the dominant cytokines expressed in situ during acute and chronic myocarditis elicited by T. cruzi. In contrast, interleukin 4 mRNA was only detected during the chronic phase. Altogether, the results indicate that the distribution of T-cell subsets in the myocardium of T. cruzi-infected mice reflects the particular profile of adhesion molecules acquired by most peripheral CD8(+) T lymphocytes and point to the possibility that multiple IFN-gamma-inducible molecules present in the inflamed tissue contribute to the establishment and maintenance of T. cruzi-induced myocarditis.
Assuntos
Linfócitos T CD8-Positivos/imunologia , Cardiomiopatia Chagásica/imunologia , Integrinas/análise , Interferon gama/farmacologia , Selectina L/análise , Antígeno-1 Associado à Função Linfocitária/análise , Receptores de Antígenos de Linfócitos T alfa-beta/análise , Receptores de Retorno de Linfócitos/análise , Animais , Moléculas de Adesão Celular/biossíntese , Cardiomiopatia Chagásica/parasitologia , Cardiomiopatia Chagásica/patologia , Quimiocinas/biossíntese , Citocinas/biossíntese , Feminino , Imunofenotipagem , Integrina alfa4beta1 , Camundongos , Camundongos Endogâmicos C3H , Miocárdio/patologia , Parasitemia/mortalidadeRESUMO
Cigarette smoking produces peripheral airway inflammation in all smokers, and chronic airways obstruction in approximately 20% of heavy smokers. The present study was designed to test the hypothesis that airways obstruction is related to changes in the expression of adhesion molecules involved in the recruitment of cells to sites of inflammation in the lung. Freshly resected lungs from heavy smokers with airways obstruction (n = 10) and from heavy smokers with normal lung function (n = 10) were collected in the operating room, inflated with optimal cutting temperature (OCT) medium and frozen over liquid nitrogen. Six micrometres thick cryostat sections cut from random samples of this tissue were stained, using immunohistochemistry, with monoclonal antibodies to the adhesion molecules on leucocytes: L-selectin, very late activation antigen-4 (VLA-4), CD11a/CD18, CD11b/CD18, CD11c/CD18; and on endothelial and epithelial surfaces: E-selectin, P-selectin, vascular cell adhesion molecule (VCAM-1), intercellular adhesion molecule (ICAM)-1 and ICAM-2 using the alkaline phosphatase anti-alkaline phosphatase (APAAP) technique. The slides were coded and the expression of each molecule scored by three observers using a semiquantitative grading system. Two inducible adhesion molecules, E-selectin on endothelium and CD11b on leucocytes, were also evaluated using quantitative morphometric analysis. The results showed a distribution of adhesion molecules that was consistent with the inflammatory response in the airways and parenchyma of all subjects but failed to show any differences between those with or without airways obstruction. We conclude that development of airways obstruction in heavy smokers cannot be explained by differences in the expression of adhesion molecules known to be involved in the control of cell traffic in the lung.
Assuntos
Moléculas de Adesão Celular/genética , Regulação da Expressão Gênica , Pneumopatias Obstrutivas/metabolismo , Fumar/metabolismo , Idoso , Anticorpos Monoclonais , Antígenos CD/análise , Antígenos CD/genética , Antígenos CD11/análise , Antígenos CD11/genética , Antígenos CD18/análise , Antígenos CD18/genética , Moléculas de Adesão Celular/análise , Selectina E/análise , Selectina E/genética , Endotélio/metabolismo , Endotélio/patologia , Epitélio/metabolismo , Epitélio/patologia , Feminino , Humanos , Imuno-Histoquímica , Integrina alfa4beta1 , Integrina beta1/análise , Integrina beta1/genética , Integrinas/análise , Integrinas/genética , Molécula 1 de Adesão Intercelular/análise , Molécula 1 de Adesão Intercelular/genética , Selectina L/análise , Selectina L/genética , Leucócitos/metabolismo , Leucócitos/patologia , Pulmão/metabolismo , Pulmão/patologia , Pneumopatias Obstrutivas/genética , Pneumopatias Obstrutivas/patologia , Masculino , Pessoa de Meia-Idade , Selectina-P/análise , Selectina-P/genética , Pneumonia/genética , Pneumonia/metabolismo , Pneumonia/patologia , Receptores de Retorno de Linfócitos/análise , Receptores de Retorno de Linfócitos/genética , Receptores de Antígeno muito Tardio/análise , Receptores de Antígeno muito Tardio/genética , Fumaça , Fumar/genética , Fumar/patologia , Molécula 1 de Adesão de Célula Vascular/análise , Molécula 1 de Adesão de Célula Vascular/genéticaRESUMO
1. CD44 is an adhesion molecule expressed by B and T lymphocytes that mediates cell attachment to extracellular matrix components and specific cell surface ligands. In normal process of T-cell development, CD44 can be implicated in homing of bone marrow-derived T-cell precursors into the thymus. In hematopoietic malignancies, CD44 and other adhesion molecules can mediate the behavior of neoplastic cells such as metastatic migration. In the leukemic process, CD44 and other adhesion molecules can mediate the behavior of neoplastic cell such as metastic migration. In the leukemic process, CD44 expression is correlated with increased numbers of circulating blasts and it is present at other sites such as the central nervous system. 2. In the present study, CD44 was investigated in lymphoblasts from 30 patients with T-cell lymphoblastic leukemia (T-ALL) and peripheral lymphocytes from 10 healthy individuals. CD44 expression was detected in 23 (77 per cent) of T-ALL cases studied and was correlated with clinical features such as mediatinal mass, adenomegaly, and infiltration of the central nervous system and other ortgans. Interestingly, CD44 expression in patient with tumor infiltration was higher than in patients with no tumor infiltration. 3. These data suggest that CD44 may be regarded as an additional marker for tumor expansion in T-cell leukemias