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Title

Junctional adhesion molecules (JAM)-B and -C contribute to leukocyte extravasation to the skin and mediate cutaneous inflammation

Authors
Ludwig, Ralf J.
Zollner, Thomas Matthias
Santoso, Sentot
Hardt, Katja
Gille, Jens
Baatz, Holger
Johann, Petra Schulze
Pfeffer, Jeannette
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Published in Journal of Investigative Dermatology. 2005, vol. 125, no. 5, p. 969-976
Abstract Leukocyte extravasation is a finely tuned process, in which transmigration is the final step. Transmigration depends on molecules located at borders of endothelial cells; e.g., junctional adhesion molecules (JAM-A, -B and -C). In vivo blockade of JAM-A lead to decreased migration of monocytes into the skin. In contrast, the role of JAM-B and -C in development of cutaneous inflammation is unknown. We therefore elicited an allergic contact dermatitis in mice using 2,4-dinitro-1-fluorobenzene. RT-PCR and immunofluorescent staining of healthy skin revealed a constitutive JAM-B (66.4%+/-6.7% of all vessels) and -C expression (88.6+/-13.2%), which remained constant after induction of contact dermatitis. Functional studies, in which either JAM-B or -C neutralizing antibodies were injected into sensitized mice prior to allergen challenge showed a concentration-dependent reduction of the contact dermatitis. Decreased ear swelling was accompanied by reduction of leukocyte infiltration as analyzed by hematoxylin and eosin (H&E) histology and enzyme activity. Combined antibody treatment at doses of 1.25 mg per kg bodyweight lead to additive inhibition of allergic contact dermatitis, indicating that JAM-B and -C may have distinct functions. In conclusion, interactions with JAM-B and -C are essential for development of cutaneous inflammation.
Keywords AnimalsAntibodies/pharmacologyCell Adhesion Molecules/antagonists & inhibitors/metabolism/*physiologyDermatitis, Allergic Contact/*immunology/metabolismEndothelium, Vascular/*immunologyImmunoglobulins/metabolism/*physiologyLeukocyte Rolling/drug effects/*immunologyLeukocytes/immunology/metabolismMembrane Proteins/antagonists & inhibitors/metabolism/*physiologyMiceMice, Inbred C57BLRNA, Messenger/analysis/metabolismSkin/immunology/metabolism
Identifiers
PMID: 16297198
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LUDWIG, Ralf J. et al. Junctional adhesion molecules (JAM)-B and -C contribute to leukocyte extravasation to the skin and mediate cutaneous inflammation. In: Journal of Investigative Dermatology, 2005, vol. 125, n° 5, p. 969-976. https://archive-ouverte.unige.ch/unige:29865

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Deposited on : 2013-09-20

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