A. Brill et al., Regulation of T-cell interaction with fibronectin by transforming growth factor-beta is associated with altered Pyk2 phosphorylation, IMMUNOLOGY, 104(2), 2001, pp. 149-156
Although the involvement of transforming growth factor-beta (TGF-beta) in i
nflammatory reactions has been extensively studied, its mode of action in t
he context of the extracellular matrix (ECM) is still not fully understood.
We undertook this study in an attempt to reveal the putative roles of TGF-
beta in T-cell adhesion and migration. We found that a 60-min treatment of
T cells with TGF-beta regulates T-cell adhesion to fibronectin (FN), a prot
otype cell adhesion protein of the ECM, depending on the presence of other
activators. At 5 pg/ml to 1 ng/ml, TGF-beta alone induced T-cell adhesion t
o FN in an integrin alpha (4)/beta (1)- and integrin alpha (5)/beta (1)-dep
endent manner. TGF-beta also attenuated T-cell migration on the stromal cel
l-derived factor (SDF)-1 alpha gradients. These effects of TGF-beta were no
t accompanied by alteration in the expression of very-late activation antig
en type 4 (VLA-4) and VLA-5, nor were they mediated by the cyclo-oxygenase
pathway. The cellular mechanism underlying the adhesion-regulating activiti
es of TGF-beta involves adhesion-associated cytoskeletal elements. TGF-beta
induced the phosphorylation of focal adhesion kinase Pyk2, but not extrace
llular signal-regulated kinase (ERK), and this effect was markedly increase
d in the presence of immobilized FN, suggesting a collaborative role for FN
-specific integrins. Indeed, TGF-beta -induced Pyk2 phosphorylation was inh
ibited by monoclonal antibodies against VLA-4, VLA-5 and CD29. Thus, TGF-be
ta, which may appear at extravascular sites during inflammation, affects th
e adhesion of T cells to ECM glycoproteins and their migration by its abili
ty to differentially induce or inhibit the phosphorylation of Pyk2.