Junctional Adhesion Molecules (JAMs) - Adhesion Molecules - page 39

Fig. 2 Cis-dimerization and trans-homophilic interaction. A: Diagram of JAM-A monomer. h e
membrane-distal and membrane-proximal Ig-domains are depicted in light grey and dark grey,
respectively. B: Membrane-bound JAM-A exists as dimer. Dimerization is mediated through a
dimerization motif in the i rst Ig-like domain which is conserved in JAM-A, -B and -C. C: JAM
dimers undergo trans-homophilic interactions.
JAMs REGULATE LEUKOCYTE-ENDOTHELIAL CELL
INTERACTIONS DURING INFLAMMATION
h e role of our immune system is to detect and eliminate pathogens or self-
modii ed components from the body. Cells of the innate immune system recognize
pathogens or self-modii ed components, which results in the eradication of the
foreign agent at the site of injury or in the initiation of the adaptive immune
response mediated by T and B cells in the draining secondary lymphoid organs.
Indeed, tissue macrophages or dendritic cells take up antigens in the periphery
and migrate to lymph nodes in which they present antigens to T cells. h is
evolutionary strategy has succeeded because the immune system has co-developed
the structures necessary to communicate between blood, tissues and lymph nodes,
namely vascular and lymphatic systems. An exquisite coordination exists between
the initiation of the inl ammatory reaction through activation of the innate
immune system and the endothelial inl ammatory response. Inl ammation results
in local modii cations in the adhesive properties of endothelial cells, which are
mediated by the upregulation of vascular adhesion molecules as well as changes
in subcellular localization of pre-existing ones. JAMs most probably belong to
this latter class of molecules, since no upregulation of JAM expression has been
reported on inl amed endothelial cells in vivo except for JAM-A or JAM-C, which
are upregulated by hyperlipidemic conditions or oxidized lipoproteins (Keiper
et al. 2005). In contrast, several studies have shown that the junctional or apical
localization of the JAM family members is af ected by inl ammatory stimulation
of endothelial cell s (Fig. 3) . h erefore, when considering the function of the JAMs
in leukocyte trai cking, one has to consider three dif erent levels of regulation: (1)
localization of the JAMs in the inter-endothelial junctions or apical surface, (2)
coupling of the JAMs with intracellular adaptors and (3) engagement of the JAMs
in trans depending on their cis-dimerization state.