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Cenicriviroc inhibits trans-endothelial passage of monocytes and is associated with impaired E-selectin expression.
D'Antoni, Michelle L; Mitchell, Brooks I; McCurdy, Sara; Byron, Mary Margaret; Ogata-Arakaki, Debra; Chow, Dominic; Mehta, Nehal N; Boisvert, William A; Lefebvre, Eric; Shikuma, Cecilia M; Ndhlovu, Lishomwa C; Baumer, Yvonne.
Afiliación
  • D'Antoni ML; Hawaii Center for HIV/AIDS, University of Hawaii, Hawaii, USA.
  • Mitchell BI; Department of Tropical Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii, USA.
  • McCurdy S; Hawaii Center for HIV/AIDS, University of Hawaii, Hawaii, USA.
  • Byron MM; Department of Tropical Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii, USA.
  • Ogata-Arakaki D; Department of Medicine, Center for Cardiovascular Research, University of Hawaii, Hawaii, USA.
  • Chow D; Hawaii Center for HIV/AIDS, University of Hawaii, Hawaii, USA.
  • Mehta NN; Department of Tropical Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii, USA.
  • Boisvert WA; Hawaii Center for HIV/AIDS, University of Hawaii, Hawaii, USA.
  • Lefebvre E; Hawaii Center for HIV/AIDS, University of Hawaii, Hawaii, USA.
  • Shikuma CM; Section of Inflammation and Cardiometabolic Diseases, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
  • Ndhlovu LC; Department of Medicine, Center for Cardiovascular Research, University of Hawaii, Hawaii, USA.
  • Baumer Y; Allergan plc, South San Francisco, California, USA.
J Leukoc Biol ; 104(6): 1241-1252, 2018 12.
Article en En | MEDLINE | ID: mdl-30088682
Incidences of cardiovascular diseases (CVD) are high among virologically suppressed HIV-infected individuals. Monocyte activation and trafficking are key mechanisms in the evolution of CVD. We studied the ability of cenicriviroc (CVC), a dual C-C chemokine receptor type 2 (CCR2) and CCR5 antagonist, to influence the migration of monocytes from HIV-infected individuals on antiretroviral therapy (ART). Monocytes were derived from 23 ART-suppressed HIV-infected and 16 HIV-uninfected donors. In a trans-endothelial migration model, monocytes, and human aortic endothelial cells (HAoECs) were exposed to cenicriviroc and migrated monocytes, quantified. Expression of CCR2 and CCR5 on monocytes and adhesion molecules (E-selectin, ICAM-1, VCAM-1, PECAM-1, and CD99) on HAoECs were measured. The single antagonists, BMS-22 (CCR2), and maraviroc (CCR5), served as controls. When both HAoECs and monocytes together were exposed to the antagonists, cenicriviroc led to a greater decrease in monocyte migration compared to BMS-22 or vehicle in both HIV-infected and HIV-uninfected groups (P < 0.05), with maraviroc having no inhibitory effect. Cenicriviroc treatment of HAoECs alone decreased monocyte migration in the HIV-infected group when compared to vehicle (P < 0.01). Inhibition of migration was not evident when monocytes alone were exposed to cenicriviroc, BMS-22 or maraviroc. Incubation of HAoECs with cenicriviroc decreased E-selectin expression (P = 0.045) but had limited effects on the other adhesion molecules. Cenicriviroc inhibits monocyte trans-endothelial migration more effectively than single chemokine receptor blockade, which may be mediated via disruption of monocyte-endothelial tethering through reduced E-selectin expression. Cenicriviroc should be considered as a therapeutic intervention to reduce detrimental monocyte trafficking.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Monocitos / Selectina E / Migración Transendotelial y Transepitelial / Antagonistas de los Receptores CCR5 / Imidazoles Tipo de estudio: Etiology_studies / Risk_factors_studies Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: J Leukoc Biol Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Monocitos / Selectina E / Migración Transendotelial y Transepitelial / Antagonistas de los Receptores CCR5 / Imidazoles Tipo de estudio: Etiology_studies / Risk_factors_studies Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: J Leukoc Biol Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido