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

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
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.

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Deposited on : 2013-09-20

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