[PMID]: | 24275118 |
[Au] Autor: | Orden S; De Pablo C; Rios-Navarro C; Martinez-Cuesta MA; Peris JE; Barrachina MD; Esplugues JV; Alvarez A |
[Ad] Endereço: | Departamento de Farmacología and CIBERehd, Facultad de Medicina, Universidad de Valencia, Valencia, Spain. |
[Ti] Título: | Efavirenz induces interactions between leucocytes and endothelium through the activation of Mac-1 and gp150,95. |
[So] Source: | J Antimicrob Chemother;69(4):995-1004, 2014 Apr. |
[Is] ISSN: | 1460-2091 |
[Cp] País de publicação: | England |
[La] Idioma: | eng |
[Ab] Resumo: | OBJECTIVES: The potential cardiovascular (CV) toxicity associated with combined antiretroviral therapy (cART) has been attributed mainly to the nucleoside reverse transcriptase inhibitors abacavir and didanosine. However, the other two components of cART--non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs)--may also be implicated, either directly or by influencing the action of the other drugs. This study evaluates the acute direct effects of the NNRTIs efavirenz and nevirapine and one of the most widely employed PIs, lopinavir, on leucocyte-endothelium interactions, a hallmark of CV disease. METHODS: Drugs were analysed in vitro in human cells (interactions of peripheral blood polymorphonuclear or mononuclear cells with human umbilical vein endothelial cells) using a flow chamber system, and in vivo in rat mesenteric vessels by means of intravital microscopy. The expression of adhesion molecules in leucocytes and endothelial cells was studied by flow cytometry, and the role of these molecules in white cell recruitment was evaluated by pre-treating human cells or rats with blocking antibodies. RESULTS: Efavirenz and nevirapine, but not lopinavir, increased the rolling flux and adhesion of leucocytes in vitro and in vivo while inducing emigration in rat venules. Efavirenz, but not nevirapine, augmented the levels of CD11b, CD11c and CD18 in neutrophils and monocytes. The actions of efavirenz, but not of nevirapine, were reversed by antibodies against Mac-1 (CD11b/CD18), gp150,95 (CD11c/CD18) or ICAM-1 (CD54). CONCLUSIONS: NNRTIs, but not PIs, interfere with leucocyte-endothelial interactions. However, differences between efavirenz and nevirapine suggest a specific CV profile for each compound. |
[Mh] Termos MeSH primário: |
Fármacos Anti-HIV/metabolismo Benzoxazinas/metabolismo Adesão Celular Endotélio/fisiologia Integrina alfaXbeta2/metabolismo Leucócitos/fisiologia Antígeno de Macrófago 1/metabolismo
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[Mh] Termos MeSH secundário: |
Animais Células Cultivadas Endotélio/efeitos dos fármacos Citometria de Fluxo Perfilação da Expressão Gênica Seres Humanos Leucócitos/efeitos dos fármacos Lopinavir/metabolismo Masculino Nevirapina/metabolismo Ratos Ratos Sprague-Dawley
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[Pt] Tipo de publicação: | JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T |
[Nm] Nome de substância:
| 0 (Anti-HIV Agents); 0 (Benzoxazines); 0 (Integrin alphaXbeta2); 0 (Macrophage-1 Antigen); 2494G1JF75 (Lopinavir); 99DK7FVK1H (Nevirapine); JE6H2O27P8 (efavirenz) |
[Em] Mês de entrada: | 1410 |
[Cu] Atualização por classe: | 140318 |
[Lr] Data última revisão:
| 140318 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 131127 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1093/jac/dkt468 |
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