Junctional adhesion molecules (JAM)-B and -C contribute to leukocyte extravasation to the skin and mediate cutaneous inflammation.
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.
Ludwig
Ralf J
RJ
Department of Dermatology, Klinikum der J.W. Goethe Universität, Frankfurt am Main, Germany. r.ludwig@em.uni-frankfurt.de
Zollner
Thomas M
TM
Santoso
Sentot
S
Hardt
Katja
K
Gille
Jens
J
Baatz
Holger
H
Johann
Petra Schulze
PS
Pfeffer
Jeannette
J
Radeke
Heinfried H
HH
Schön
Michael P
MP
Kaufmann
Roland
R
Boehncke
Wolf-Henning
WH
Podda
Maurizio
M
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D017449:Dermatitis, Allergic Contact / Q000276:immunology* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000276:immunology*; D007136:Immunoglobulins / Q000378:metabolism / Q000502:physiology*; D036904:Leukocyte Rolling / Q000187:drug effects / Q000276:immunology*; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D012867:Skin / Q000276:immunology / Q000378:metabolism; D062765:Junctional Adhesion Molecule B
D000906:Antibodies; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D008565:Membrane Proteins; D012333:RNA, Messenger; C498781:Jam2 protein, mouse; D062765:Junctional Adhesion Molecule B; C486723:Jam3 protein, mouse