Figure 2A
Schematic representation of the modulation of integrin expression,
matrix degrading proteinases and matrix binding in T cells upon alpha4beta1/VCAM-1
mediated adhesion to and transmigration through endothelial cells. Following
engagement of alpha4beta1by endothelial cell VCAM-1, the T cell exhibits
down-regulation of its expression of alpha4beta1and LFA-1 and up-regulation
of its expression of pro-MMP-2 (72 kDa gelatinase). This is followed by
formation and clustering of a tertiary complex comprised of MT1-MMP, TIMP-2
and pro-MMP-2 and activation of MMP-2. In addition, these T cells exhibit
reduced adhesion to VCAM-1 and ICAM-1 and increased adhesion to collagen
types I and IV, fibronectin and laminin. Also noted were increases in
endothelial cell uPA expression and activity and decreases in endothelial
cell PAI-1 expression following engagement of VCAM-1 by alpha4beta1.
Figure 2B
Schematic illustrating the tethering, association
and signaling properties of MT1-MMP and CD44 on the cell surface. Upon
induction of autoimmune encephalomyelitis, MT1-MMP (MMP-14) expression,
localization and activities are modulated and effect the expression levels,
activities and functions of CD44, MMP-2, -9 and possibly other MMPs (MMP-7),
cleavage of adhesion molecules, ECM components (blue arrows) and chemokines & cytokines
(red arrows), thus affecting a wide range of epithelial, lymphocytic and
endothelial cell behaviors.