RESUMO
Thirty patients with clinically isolated syndromes (CIS) were evaluated at the onset of neurological symptoms and when they developed clinically definite MS (CDMS). Surface expression of LFA-1alpha, VLA-4 and intercellular adhesion molecule-1 (ICAM-1) on PBMC and CSF cells was evaluated using flow cytometry. Serum and CSF concentrations of soluble vascular cell adhesion molecules-1 (VCAM-1), ICAM-1 and E-Selectin, as well as MMP-9 and MMP-2 serum concentrations were assayed using ELISA. Surface expression of LFA-1alpha and VLA-4 molecules on peripheral blood and CSF T cells and monocytes from CIS and CDMS was significantly increased compared with control subjects. Moreover, LFA-1alpha and VLA-4 expression was significantly higher in patients who developed CDMS compared with those with CIS. Similar changes were observed in the serum levels of MMP-9. Furthermore, patients with CIS and CDMS had significantly higher levels of CSF sVCAM and s-E-Selectin than control subjects. These data suggest that VLA-4, LFA-1alpha and MMP-9 play a leading role in the evolution of inflammatory demyelinating lesions in patients with CIS who develop CDMS.
Assuntos
Moléculas de Adesão Celular/biossíntese , Metaloproteinases da Matriz/biossíntese , Esclerose Múltipla/enzimologia , Esclerose Múltipla/metabolismo , Adulto , Moléculas de Adesão Celular/sangue , Moléculas de Adesão Celular/líquido cefalorraquidiano , Membrana Celular/enzimologia , Membrana Celular/metabolismo , Feminino , Humanos , Integrina alfa4beta1/biossíntese , Integrina alfa4beta1/sangue , Molécula 1 de Adesão Intercelular/biossíntese , Molécula 1 de Adesão Intercelular/sangue , Molécula 1 de Adesão Intercelular/líquido cefalorraquidiano , Estudos Longitudinais , Antígeno-1 Associado à Função Linfocitária/biossíntese , Antígeno-1 Associado à Função Linfocitária/sangue , Antígeno-1 Associado à Função Linfocitária/líquido cefalorraquidiano , Masculino , Metaloproteinase 2 da Matriz/biossíntese , Metaloproteinase 2 da Matriz/sangue , Metaloproteinase 9 da Matriz/biossíntese , Metaloproteinase 9 da Matriz/sangue , Metaloproteinases da Matriz/sangue , Pessoa de Meia-Idade , Monócitos/enzimologia , Monócitos/metabolismo , Esclerose Múltipla/sangue , Esclerose Múltipla/líquido cefalorraquidiano , Solubilidade , Subpopulações de Linfócitos T/enzimologia , Subpopulações de Linfócitos T/metabolismo , Fatores de Tempo , Regulação para CimaRESUMO
OBJECTIVE: Messier L-selectin and LFA-1 in neutrophils from moderate and non atopic asthma patients, before and after stimuli with and without Sa (Staphylococcus aureus). MATERIALS AND METHOD: Design Trial; experimental. We studied neutrophils from 12 moderate and non atopic asthma patients and 12 healthy subjects before and after stimuli with and without Sa. MEASURES: The neutrophyls adhesion molecules, CD 62-L and CD 11 a was measured by citometric flow assays. RESULTS: The median of CD 62-L molecule expression increase with the stimuli in non atopic asthma patients from 2444 (CI 1966, CS 3627, RC 1661) to 6285.5 (CI 5243, CS 7203, RC 1960), and the median of CD 11 a molecule expression decrease with the stimuli in non atopic asthma patients from 9910.5 (CI 9765, CS 9961, RC 196) to 7670 (CI 7125, CS 8291, RC 1166). The median of CD 11 a molecule expression increase with the stimuli in healthy subjects from 593 (CI 361, CS 929, RC 568) to 1113 (CI 910, CS 1240, RC 330) and the median of CD 11 a molecule expression decrease with the stimuli in healthy subjects from 9850 (CI 9741, CS 9898, RC 157) to 9808.5 (CI 9693, CS 9890, RC 197) [CI. Inferior Cuartil, CS. Superior Cuartil, RC.-Cuartil Range].
Assuntos
Asma/sangue , Selectina L/biossíntese , Antígeno-1 Associado à Função Linfocitária/biossíntese , Neutrófilos/metabolismo , Staphylococcus aureus , Proteínas de Bactérias/farmacologia , Antígenos CD11/biossíntese , Humanos , Neutrófilos/efeitos dos fármacosRESUMO
Interactions between immunocompetent cells require the participation of T cell antigen receptor (TCR) and the integrin lymphocyte function-associated molecule-1 (LFA-1, CD11a/CD18). These interactions are mediated by interlinking cytokines, which are important in determining the type of immune response. In the present study, we have shown that in American cutaneous leishmaniasis (ACL) lesions, most infiltrating T cells expressed the alpha beta TCR including those selectively migrating to the epidermis. In contrast, gamma delta T cells were abundant in localized (LCL) and scarce in muco-cutaneous (MCL) and diffuse (DCL) cutaneous leishmaniasis, suggesting a role in effective granulomas. There were differences in the expression of LFA-1 alpha and beta subunits, with most cells expressing LFA-1 beta. The ratio LFA-1 beta/LFA-1 alpha was higher in LCL (11.8:1) than in MCL (3.3:1) and DCL (2.4:1). Similar results were observed in Leishmania mexicana-infected C57BL/6 mice. DCL lesions showed a higher proportion of LFA-1 alpha+ cells than MCL and LCL lesions. A reverse-transcriptase polymerase chain reaction (RT-PCR) analysis of the cytokine profiles showed that most T cells present in the MCL and DCL lesions secrete a mixture of Type 1 and Type 2 cytokine patterns, but in DCL granulomas predominate the Type 2 cytokines. In LCL the cytokine patterns show a preponderance of INF gamma over IL-4, and low levels of IL-5 and IL-10, suggesting a Type 1 cytokine profile.
Assuntos
Leishmaniose Cutânea/imunologia , Linfocinas/biossíntese , Pele/imunologia , Subpopulações de Linfócitos T/imunologia , Animais , Anticorpos Monoclonais , Moléculas de Adesão Celular/biossíntese , Feminino , Granuloma/imunologia , Humanos , Leishmaniose Tegumentar Difusa/imunologia , Leishmaniose Mucocutânea/imunologia , Antígeno-1 Associado à Função Linfocitária/biossíntese , Linfocinas/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase , DNA Polimerase Dirigida por RNA , Receptores de Antígenos de Linfócitos T/biossíntese , Linfócitos T/imunologiaRESUMO
Interactions between immunocompetent cells require the participation of T cell antigen receptor (TCR) and the integrin lymphocyte function-associated molecule-1 (LFA-1, CD11a/CD18). These interactions are mediated by interlinking cytokines, which are important in determining the type of immune response. In the present study, we have shown that in American cutaneous leishmaniasis (ACL) lesions, most infiltrating T cells expressed the alpha beta TCR including those selectively migrating to the epidermis. In contrast, gamma delta T cells were abundant in localized (LCL) and scarce in muco-cutaneous (MCL) and diffuse (DCL) cutaneous leishmaniasis, suggesting a role in effective granulomas. There were differences in the expression of LFA-1 alpha and beta subunits, with most cells expressing LFA-1 beta. The ratio LFA-1 beta/LFA-1 alpha was higher in LCL (11.8:1) than in MCL (3.3:1) and DCL (2.4:1). Similar results were observed in Leishmania mexicana-infected C57BL/6 mice. DCL lesions showed a higher proportion of LFA-1 alpha+ cells than MCL and LCL lesions. A reverse-transcriptase polymerase chain reaction (RT-PCR) analysis of the cytokine profiles showed that most T cells present in the MCL and DCL lesions secrete a mixture of Type 1 and Type 2 cytokine patterns, but in DCL granulomas predominate the Type 2 cytokines. In LCL the cytokine patterns show a preponderance of INF gamma over IL-4, and low levels of IL-5 and IL-10, suggesting a Type 1 cytokine profile