Junctional Adhesion Molecules (JAM)-B and -C Contribute to Leukocyte Extravasation to the Skin and Mediate Cutaneous Inflammation

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.

Caspase-1–Independent IL-1 Release Mediates Blister Formation in Autoantibody-Induced Tissue Injury through Modulation of Endothelial Adhesion Molecules

“…In this bullous pemphigoid model, detailed analysis of the neutrophil inflammatory response revealed that CD11a was necessary for neutrophil recruitment, whereas CD11b mediated late neutrophil accumulation and neutrophil apoptosis (35). In addition, neutrophil recruitment into the skin also was shown to depend on additional adhesion molecules, including selectins (36), and on junctional adhesion molecules (20). Hence, it is tempting to speculate that blockade of adhesion molecules might also protect mice from blister formation in experimental EBA.…”

“…The extent of leukocyte infiltration was scored semiquantitatively in a blinded fashion, as described previously (20). Direct IF microscopy for the detection of rabbit IgG and murine C3 in experimental EBA was performed on 6-mm cryosections, as described, using goat anti-rabbit IgG (Dako) and goat anti-murine C3 (MP Biomedicals, Kaysersberg, France), both labeled with FITC.…”

CD99 Is a Key Mediator of the Transendothelial Migration of Neutrophils

“…Several reports suggest JAM-A mediates TEM of leukocytes (41,42), although the transmigration of human neutrophils (11) and monocytes (10) in vitro is unaffected by anti-JAM-A mAb. JAM-B and -C have been implicated in leukocyte extravasation in vitro and in vivo (43)(44)(45). Poliovirus receptor is a member of a related family of junctional proteins on EC and binds to CD226 on leukocytes.…”

The Blood–Brain Barrier

“…JAMs are immunoglobulin superfamily members that form homotypic interactions at tight junctions in epithelial cells and ECs. JAMs have been shown to regulate leukocyte extravasation as well as paracellular permeability (Martin-Padura et al 1998;Johnson-Leger et al 2002;Ludwig et al 2005). In particular, JAM4 has been identified at the BBB in mice (Daneman et al 2010a).…”