Shedding of PECAM-1 during HIV infection: A potential role for soluble PECAM-1 in the pathogenesis of NeuroAIDS

Eliseo Eugenin, R. Gamss, C. Buckner, D. Buono, R. S. Klein, E. E. Schoenbaum, T. M. Calderon, J. W. Berman

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Human immunodeficiency virus (HIV) infection is characterized by viral entry into the central nervous system (CNS), which is mediated, in part, by the transmigration of HIV-infected monocytes into the brain. The elaboration of chemokines and other factors by these infected cells contributes to CNS inflammation and cognitive impairment in a significant number of HIV-infected individuals. Recently, we demonstrated that HIV-infected monocyte transmigration into the CNS is enhanced greatly by the chemokine CC chemokine ligand 2 (CCL2)/monocyte chemoattractant protein-1. Platelet endothelial cell adhesion molecule-1 (PECAM-1) plays an important role in leukocyte transmigration across the endothelium of the systemic vasculature by mediating homophilic interactions between endothelial cells (EC)-EC and EC-leukocytes, thus preserving vessel integrity. The role of PECAM-1 in HIV-infected leukocyte transmigration across the blood brain barrier (BBB) and NeuroAIDS has not been characterized. We demonstrate that in brain tissue from individuals with HIV encephalitis, there is an accumulation of cleaved, soluble forms of the extracellular region of PECAM-1 (sPECAM-1). In addition, HIV-infected individuals have elevated levels of sPECAM-1 in their sera. Our in vitro data demonstrate that HIV-infected leukocytes, when treated with CCL2, shed sPECAM-1, suggesting a mechanism of extracellular PECAM-1 cleavage and release dependent on HIV infection and CCL2. We hypothesize that sPECAM-1 production by HIV-infected leukocytes, resulting in the accumulation of sPECAM-1 within the CNS vasculature and the generation of truncated, intracellular forms of PECAM-1 within leukocytes, alters PECAM-1 interactions between EC-EC and EC-leukocytes, thus contributing to enhanced transmigration of HIV-infected leukocytes into the CNS and changes in BBB permeability during the pathogenesis of NeuroAIDS.

Original languageEnglish (US)
Pages (from-to)444-452
Number of pages9
JournalJournal of Leukocyte Biology
Volume79
Issue number3
DOIs
StatePublished - Mar 1 2006
Externally publishedYes

Fingerprint

CD31 Antigens
Virus Diseases
HIV
Leukocytes
Endothelial Cells
Central Nervous System
CC Chemokines
Ligands
Blood-Brain Barrier
Chemokines
Monocytes
Chemokine CCL2
Brain
Encephalitis
Endothelium
Permeability

Keywords

  • CCL2
  • Encephalitis
  • Leukocytes
  • Transmigration

ASJC Scopus subject areas

  • Immunology
  • Cell Biology

Cite this

Shedding of PECAM-1 during HIV infection : A potential role for soluble PECAM-1 in the pathogenesis of NeuroAIDS. / Eugenin, Eliseo; Gamss, R.; Buckner, C.; Buono, D.; Klein, R. S.; Schoenbaum, E. E.; Calderon, T. M.; Berman, J. W.

In: Journal of Leukocyte Biology, Vol. 79, No. 3, 01.03.2006, p. 444-452.

Research output: Contribution to journalArticle

Eugenin, E, Gamss, R, Buckner, C, Buono, D, Klein, RS, Schoenbaum, EE, Calderon, TM & Berman, JW 2006, 'Shedding of PECAM-1 during HIV infection: A potential role for soluble PECAM-1 in the pathogenesis of NeuroAIDS', Journal of Leukocyte Biology, vol. 79, no. 3, pp. 444-452. https://doi.org/10.1189/jlb.0405215
Eugenin, Eliseo ; Gamss, R. ; Buckner, C. ; Buono, D. ; Klein, R. S. ; Schoenbaum, E. E. ; Calderon, T. M. ; Berman, J. W. / Shedding of PECAM-1 during HIV infection : A potential role for soluble PECAM-1 in the pathogenesis of NeuroAIDS. In: Journal of Leukocyte Biology. 2006 ; Vol. 79, No. 3. pp. 444-452.
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