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Zhang X, Jiang S, Yu J, et al. Cocaine enhances HIV-1 gp120-induced lymphatic endothelial dysfunction in the lung. Physiol Rep. 2015;3(8)doi: 10.14814/phy2.12482.
Zhang, X., Jiang, S., Yu, J., Kuzontkoski, P. M., & Groopman, J. E. (2015). Cocaine enhances HIV-1 gp120-induced lymphatic endothelial dysfunction in the lung. Physiological reports, 3(8), . https://doi.org/10.14814/phy2.12482
Zhang, Xuefeng, et al. "Cocaine enhances HIV-1 gp120-induced lymphatic endothelial dysfunction in the lung." Physiological reports vol. 3,8 (2015). doi: https://doi.org/10.14814/phy2.12482
Zhang X, Jiang S, Yu J, Kuzontkoski PM, Groopman JE. Cocaine enhances HIV-1 gp120-induced lymphatic endothelial dysfunction in the lung. Physiol Rep. 2015 Aug;3(8). doi: 10.14814/phy2.12482. PMID: 26311830; PMCID: PMC4562568.
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Physiol Rep. 2015 Aug;3(8). doi: 10.14814/phy2.12482.

Cocaine enhances HIV-1 gp120-induced lymphatic endothelial dysfunction in the lung.

Physiological reports

Xuefeng Zhang, Susan Jiang, Jinlong Yu, Paula M Kuzontkoski, Jerome E Groopman

Affiliations

  1. Division of Experimental Medicine, Beth Israel Deaconess Medical Center Harvard Medical School, Boston, Massachusetts, USA.
  2. Division of Experimental Medicine, Beth Israel Deaconess Medical Center Harvard Medical School, Boston, Massachusetts, USA Department of Psychiatry, Mclean Hospital Harvard Medical School, Belmont, Massachusetts, USA.
  3. Division of Experimental Medicine, Beth Israel Deaconess Medical Center Harvard Medical School, Boston, Massachusetts, USA DynaMed, EBSCO Information Services, Ipswich, Massachusetts, USA.
  4. Division of Experimental Medicine, Beth Israel Deaconess Medical Center Harvard Medical School, Boston, Massachusetts, USA [email protected].

PMID: 26311830 PMCID: PMC4562568 DOI: 10.14814/phy2.12482

Abstract

Pulmonary complications are common in both AIDS patients and cocaine users. We addressed the cellular and molecular mechanisms by which HIV and cocaine may partner to induce their deleterious effects. Using primary lung lymphatic endothelial cells (L-LECs), we examined how cocaine and HIV-1 gp120, alone and together, modulate signaling and functional properties of L-LECs. We found that brief cocaine exposure activated paxillin and induced cytoskeletal rearrangement, while sustained exposure increased fibronectin (FN) expression, decreased Robo4 expression, and enhanced the permeability of L-LEC monolayers. Moreover, incubating L-LECs with both cocaine and HIV-1 gp120 exacerbated hyperpermeability, significantly enhanced apoptosis, and further impaired in vitro wound healing as compared with cocaine alone. Our studies also suggested that the sigma-1 receptor (Sigma-1R) and the dopamine-4 receptor (D4R) are involved in cocaine-induced pathology in L-LECs. Seeking clinical correlation, we found that FN levels in sera and lung tissue of HIV(+) donors were significantly elevated as compared to HIV(-) donors. Our in vitro data demonstrate that cocaine and HIV-1 gp120 induce dysfunction and damage of lung lymphatics, and suggest that cocaine use may exacerbate pulmonary edema and fibrosis associated with HIV infection. Continued exploration of the interplay between cocaine and HIV should assist the design of therapeutics to ameliorate HIV-induced pulmonary disorders within the drug using population.

© 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Keywords: Cocaine; D4 receptor; HIV; fibronectin; lymphatic endothelial cells; sigma‐1 receptor

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