Transendothelial migration of CD16+ monocytes in response to fractalkine under constitutive and inflammatory conditions

Petronela Ancuta, Ashlee Moses, Dana Gabuzda

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

CD16+ monocytes represent 5-10% of circulating monocytes in healthy individuals and are dramatically expanded in several pathological conditions including AIDS and HIV-1-associated dementia (HAD). CD16+ monocytes constitutively produce high levels of pro-inflammatory cytokines and neurotoxic factors that may contribute to the pathogenesis of these disorders. Monocyte recruitment into the central nervous system (CNS) and other peripheral tissues in response to locally produced chemokines is a critical event in immune surveillance and inflammation and involves monocyte arrest onto vascular beds and subsequent diapedesis. Here we investigate the ability of CD16+ monocytes to undergo transendothelial migration (TEM) under constitutive and inflammatory conditions. CD16+ monocytes underwent TEM across unstimulated human umbilical vascular (HUVEC) and brain microvascular endothelial (BMVEC) cell monolayers in response to soluble fractalkine (FKN/CX3CL1). Stimulation with tumor necrosis factor (TNF) and interferon-γ (IFN-γ) induced high and low expression of membrane-bound FKN on HUVEC and BMVEC, respectively, together with expression of VCAM-1 and intercellular adhesion molecule-1 (ICAM)-1. By contrast, only HUVEC expressed CD62E while BMVEC remained negative. Both CD16- and CD16+ monocyte subsets adhered to TNF/IFN-γ-stimulated HUVEC with higher frequency than to unstimulated HUVEC. Monocyte chemoattractant protein-1 (MCP-1) triggered efficient TEM of CD16- monocytes across TNF/IFN-γ-stimulated HUVEC, whereas soluble FKN failed to induce TEM of CD16+ monocytes across stimulated HUVEC. These results demonstrate that stimulation with TNF and IFN-γ triggers expression of membrane-bound FKN on both HUVEC and BMVEC, but prevents TEM of CD16+ monocytes in response to soluble FKN. Thus, proinflammatory CD16+ monocytes may contribute to the pathogenesis of HAD and other inflammatory CNS diseases by affecting the integrity of the blood-brain barrier as a consequence of their massive accumulation onto inflamed brain vascular endothelial cells expressing FKN and other adhesion molecules.

Original languageEnglish (US)
Pages (from-to)11-20
Number of pages10
JournalImmunobiology
Volume209
Issue number1-2
DOIs
StatePublished - 2004

Fingerprint

Chemokine CX3CL1
Transendothelial and Transepithelial Migration
Monocytes
Interferons
Tumor Necrosis Factor-alpha
Blood Vessels
Dementia
HIV-1
Endothelial Cells
Umbilicus
Aptitude
Membranes
Vascular Cell Adhesion Molecule-1
Chemokine CCL2
Central Nervous System Diseases
Brain
Intercellular Adhesion Molecule-1
Blood-Brain Barrier
Chemokines

Keywords

  • Dendritic cells
  • Monocytes
  • Siglecs

ASJC Scopus subject areas

  • Immunology

Cite this

Transendothelial migration of CD16+ monocytes in response to fractalkine under constitutive and inflammatory conditions. / Ancuta, Petronela; Moses, Ashlee; Gabuzda, Dana.

In: Immunobiology, Vol. 209, No. 1-2, 2004, p. 11-20.

Research output: Contribution to journalArticle

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