alexa Mechanisms by which chronic ethanol feeding impairs the migratory capacity of cutaneous dendritic cells.
Pathology

Pathology

Journal of Clinical & Experimental Pathology

Author(s): Parlet CP, Schlueter AJ

Abstract Share this page

Abstract BACKGROUND: Chronic alcoholism is associated with increased incidence and severity of skin infection. Cutaneous dendritic cells (CDCs) play a pivotal role in skin immunity, and chronic ethanol (EtOH) feeding in mice has been shown to inhibit CDC migration to skin-draining lymph nodes (dLNs) following epicutaneous sensitization. Because CDC subsets differentially initiate T-cell responses, it is important to determine how EtOH feeding affects migration of each subset and identify mechanisms responsible for observed defects. METHODS: Mice received EtOH in the drinking water for ≥ 16 weeks. Baseline numbers of CDC subsets and their migration to the dLNs following fluorescein 5-isothiocyanate (FITC) sensitization were assessed by flow cytometry. Epidermal cell suspension and skin explant cultures were used to measure the impact of EtOH upon molecules that influence CDC migration. Cytokine arrays performed on explant culture supernatants assessed local production of inflammatory cytokines. RESULTS: Chronic EtOH feeding reduced migration of all CDC subsets to the dLNs following FITC sensitization. Reduced migration of dermal-resident CDCs did not correspond with reduced baseline numbers of these cells. For Langerhans cells (LCs), EtOH-induced migratory dysfunction corresponded with delayed down-regulation of E-cadherin, chemokine receptor 1 (CCR1), and CCR6 and impaired up-regulation of matrix metalloproteinases (MMPs) 2 and 9. In skin explant assays, EtOH blunted CDC mobilization following stimulation with CCL21/CPG 1826. No alteration in CD54 or CCR7 expression was observed, but production of skin-derived tumor necrosis factor alpha (TNF-α) was reduced. Poor migratory responses in vitro could be improved by supplementing explant cultures from EtOH-fed mice with TNF-α. CONCLUSIONS: Chronic EtOH consumption does not alter baseline dermal-resident CDC numbers. However, like LCs, migratory responsiveness of dermal CDCs was decreased following FITC sensitization. Inefficient down-regulation of both CCRs and adhesion molecules and the inability to up-regulate MMPs indicate that EtOH impedes LC acquisition of a promigratory phenotype. These defects, combined with improvement of the migratory defect with in vitro TNF-α replacement, demonstrate intrinsic as well as environmental contributions to defective CDC migration. These findings provide novel mechanisms to explain the observed increased incidence and severity of skin infections in chronic alcoholics. Copyright © 2013 by the Research Society on Alcoholism.
This article was published in Alcohol Clin Exp Res and referenced in Journal of Clinical & Experimental Pathology

Relevant Expert PPTs

Relevant Speaker PPTs

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri, Food, Aqua and Veterinary Science Journals

Dr. Krish

[email protected]

1-702-714-7001 Extn: 9040

Clinical and Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemical Engineering and Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001 Extn: 9040

Earth & Environmental Sciences

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

General Science and Health care Journals

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics and Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001 Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Informatics Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Material Sciences Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Mathematics and Physics Journals

Jim Willison

[email protected]

1-702-714-7001 Extn: 9042

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001 Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

John Behannon

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001 Extn: 9042

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords