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167 REGULATION OF INNATE AND ADAPTIVE IMMUNE RESPONSES BY HUMAN ARTERIES.
  1. O. Pryshchep,
  2. W. Ma-Krupa,
  3. K. Shimada,
  4. A. Vaglio,
  5. J. J. Goronzy,
  6. C. M. Weyand
  1. Lowance Center for Human Immunology, Emory University School of Medicine, Atlanta, GA

Abstract

Purpose Human medium-sized and large arteries possess a population of dendritic cells (DCs) that are localized at the media-adventitia border. The physiologic role of such DCs is unknown. DCs are typically equipped with pattern-recognition receptors, such as Toll-like receptors (TLR) that detect "danger " and initiate immune responses. We have explored whether arteries from different vascular territories express TLR and whether stimulation with TLR ligands, such as LPS, is sufficient to trigger vascular inflammation.

Methods Human medium-sized and large arteries were collected from 6 vascular beds (temporal, carotid, subclavian, mesenteric, iliac, and thoracic aorta) of 21 donors (mean age 65 years). Samples with atherosclerotic plaque and inflammatory infiltrates by histology were excluded. Transcripts of TLR1-9 and the DC marker CD11c were quantified by real-time PCR. Distribution of vascular DC was examined by immunohistochemistry. Responsiveness of human arteries to the TLR ligand LPS was tested by implanting SCID mice with human artery pieces, injecting 3 mg LPS and adoptively transferring 5 3 106 human T cells. Explanted artery grafts were examined for inflammation.

Results All human arteries contained transcripts for TLR1-7 and TLR9. TLR8 was present in some but not all vascular territories. Notably, each vascular bed expressed a unique TLR pattern. Patterns of TLR expression were similar in carotid and iliac arteries. Temporal arteries, the preferred target for giant cell arteritis, were distinct from all other vessels and were characterized by prominent expression of TLR2 and TLR8. Remarkably, the aortic wall had the lowest transcript levels for TLR. In the human artery-SCID chimeras (n = 8), bloodborne LPS was sufficient to induce recruitment and activation of adoptively transferred T cells, forming inflammatory infiltrates in the vessel wall.

Conclusion Human medium-sized and large arteries have functional similarities to lymphoid organs in that they recognize and respond to pathogen-derived molecules. DCs in the vascular wall attract and retain T lymphocytes and initiate early events in vascular inflammation. Target tissue susceptibility with particular arteries being susceptible to selected vasculopathies may relate to the immune functions of DC displaying site-specific networks in different vascular beds.

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