Junctional Adhesion Molecules (JAMs) - Adhesion Molecules - page 40

Fig. 3 Putative molecular interaction network of JAMs and integrins involved in leukocyte trans-
endothelial migration. Grey boxes: Proteins exclusively expressed on circulating cells. Spot ed
grey boxes: Proteins expressed on both circulating and endothelial cells. White boxes: Proteins
exclusively expressed on endothelial cells.
Evidence for a relocalization of JAM-A during inl ammation came from studies
with cultured endothelial cells in which combined treatment with IFN-γ and
TNF-α results in JAM-A localization to the apical membrane domain, where it can
serve as counter-receptor for the leukocyte integrin α L β 2 (Weber et al. 2007). h ese
results coni rmed the pioneering work by E. Dejana and coworkers demonstrating
that JAM-A was essential for monocyte trans-endothelial migration in vitro and
that treatment of mice with anti-JAM-A mAbs inhibits leukocyte recruitment in
air pouch model and in cytokine-induced meningitis (Martin-Padura et al. 1998).
Although the studies on JAM-A paved the way for understanding the function of
JAM-B and JAM-C in leukocyte migration, the latter members of the family dif er
from JAM-A in terms of tissue distribution and inl ammatory regulation. Indeed,
JAM-B has been initially identii ed as an adhesion molecule highly expressed on
High Endothelial Venules (HEVs) and later as a vascular ligand for JAM-C, which
is also expressed on human leukocytes and platelets. JAM-C has been found to be
transported from intracellular stores to the surface of human dermal microvascular
endothelial cells upon VEGF or histamine stimulation (Orlova et al. 2006). Based
on the pleiotropic homo- and heterophilic interactions of JAMs, many research
groups focused on the adhesive function of the JAM proteins and their role during
leukocyte trans-endothelial or trans-epithelial migration (Weber et al. 2007).