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Clin Dev Immunol. 2013;2013:617809. doi: 10.1155/2013/617809. Epub 2013 Dec 12.

Expression and function of the homeostatic molecule Del-1 in endothelial cells and the periodontal tissue.

Author information

1
Department of Microbiology, School of Dental Medicine, University of Pennsylvania, 240 South 40th Street, Philadelphia, PA 19104, USA.
2
Department of Microbiology, School of Dental Medicine, University of Pennsylvania, 240 South 40th Street, Philadelphia, PA 19104, USA ; Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109, USA.
3
Oral Health and Systemic Disease Research Group, University of Louisville School of Dentistry, Louisville, KY 40292, USA.
4
Division of Vascular Inflammation, Diabetes and Kidney, Department of Medicine, Technical University Dresden, 01307 Dresden, Germany ; Department of Clinical Pathobiochemistry and Institute for Clinical Chemistry and Laboratory Medicine, Technical University Dresden, 01307 Dresden, Germany.

Abstract

Developmental endothelial locus-1 (Del-1) is an endothelial cell-secreted protein that limits the recruitment of neutrophils by antagonizing the interaction between the LFA-1 integrin on neutrophils and the intercellular adhesion molecule (ICAM)-1 on endothelial cells. Mice with genetic or age-associated Del-1 deficiency exhibit increased neutrophil infiltration in the periodontium resulting in inflammatory bone loss. Here we investigated additional novel mechanisms whereby Del-1 could interfere with neutrophil recruitment and inflammation. Treatment of human endothelial cells with Del-1 did not affect the expression of endothelial molecules involved in the leukocyte adhesion cascade (ICAM-1, VCAM-1, and E-selectin). Moreover, genetic or age-associated Del-1 deficiency did not significantly alter the expression of these adhesion molecules in the murine periodontium, further ruling out altered adhesion molecule expression as a mechanism whereby Del-1 regulates leukocyte recruitment. Strikingly, Del-1 inhibited ICAM-1-dependent chemokine release (CXCL2, CCL3) by neutrophils. Therefore, Del-1 could potentially suppress the amplification of inflammatory cell recruitment mediated through chemokine release by infiltrating neutrophils. Interestingly, Del-1 was itself regulated by inflammatory stimuli, which generally exerted opposite effects on adhesion molecule expression. The reciprocal regulation between Del-1 and inflammation may contribute to optimally balance the protective and the potentially harmful effects of inflammatory cell recruitment.

PMID:
24416060
PMCID:
PMC3876683
DOI:
10.1155/2013/617809
[Indexed for MEDLINE]
Free PMC Article

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