Collagen receptor on T lymphocytes and the control of lymphocyte motility

Abstract

Human lymphocytes, freshly isolated from blood, were allowed to settle on surfaces coated by collagen type 1, fibronectin, laminin, IgG or albumin at different concentrations. In separate cultures the lymphocytes were also exposed to these proteins in soluble form. The lymphocytes, predominantly T cells, attached to two-dimensional collagen substrata both in the presence and absence of serum but did not adhere or adhered poorly to substrata coated with fibronectin, laminin, IgG and albumin. In contrast, T blasts induced in a mixed lymphocyte culture adhered to fibronectin-coated substratum. During contact with substratum-bound collagen for a 24-h period, 47 +/- 15% of the freshly purified lymphocytes from separate individuals developed motile behavior whereas 16 +/- 4% of the cells became motile on fibronectin. Gelatin (denatured collagen) also mediated attachment of lymphocytes to surfaces but only at comparatively high concentrations (40 mg/ml). Collagen and gelatin in solution also caused agglutination and motility of the vast majority of freshly isolated T lymphocytes whereas fibronectin and other proteins, when presented in soluble form, did not. Cell agglutination was maximal at moderate (10 or 20 mg/ml) and cell motility at low gelatin concentrations (1 to 10 mg/ml). High gelatin concentrations (20 and 40 mg/ml) did not induce motile behavior. Cytochalasin B augmented the proportion of adherent cells on gelatin-coated substrata. In the presence of cytochalasin B gelatin mediated substrate-adhesion at concentrations below those which normally induced adhesion indicating that motile behavior counteracted persistent lymphocyte adhesion to the substratum. Noteworthy, gelatin/collagen is unique among ligands (e.g. plasma fibronectin and other serum proteins) in its capacity to induce motility in the vast majority of resting lymphocytes freshly isolated from blood within a relatively short period. Taken together these results indicate that circulating lymphocytes have a collagen/gelatin-binding plasma membrane component. Cross-linking of this component is a likely explanation for the selective inducing effect of gelatin and collagen on lymphocyte motility. The present results showed that the lymphocyte plasma membrane contains collagen-binding components with a relative molecular mass of 130 and 55 kDa. The 55-kDa component also reacted with an anti-fibronectin antibody. Thus, interactions with the extracellular matrix may control lymphocyte locomotor capacity.

VLA‐2 is the integrin used as a collagen receptor by leukocytes

“…A previous report of a "130-kDa" collagen-binding lymphocyte membrane molecule may also have beenVLA-2 [9]. It has been known for some time that platelet VLA-2 specifically binds collagen [ll, 12].We show here that either on intact cells or in cell lysates,VLA-2 is the integrin used by Tcells as a collagen-binding receptor.…”

“…For example, collagen enhances phagocytic function of monocytes via activation of CR and FcyR [7] and over a longer time period, causes differentiation of monocytes [8]. Tcells in contact with collagen for a 24 h period develop motile behavior [9] and collagen has also been suggested to provide a costimulus for CD3-mediated T cell proliferation [lo].…”

The invasive and destructive behavior of HIV-induced T cell syncytia on collagen and endothelium

“…Lymphocytes have also been demonstrated to express a receptor for collagen [43][44][45], to adhere to collagen [43][44][45][46], and to disrupt and degrade collagen matrices [46][47][48][49][50]. Here, we have demonstrated that approximately half of the cells in a SUP-T1 population actively translocated across the surface of a dehydrated or hydrated collagen gel and that cells readily penetrated hydrated collagen gels.…”

“…Lymphocytes have been demonstrated to invade collagen gels [41,42] and collagen has been demonstrated to enhance leukocyte motility [42,43]. Lymphocytes have also been demonstrated to express a receptor for collagen [43][44][45], to adhere to collagen [43][44][45][46], and to disrupt and degrade collagen matrices [46][47][48][49][50].…”

Up-regulated β1-integrin expression in autoimmune thyroid disorders

“…Moreover, ECM components can modulate lymphocyte functions through specific interactions, possibly mediated by VLA integrins [40,41]. This accumulation of ECM proteins in AITD, caused by high density of specific VLA receptors, may not only serve to anchor T cells to different components of the ECM, but also be a strong stimulus to intrathyroidal lymphocytes, enhancing proliferation and motility of these cells [42].…”