Lymphocyte-endothelial cell interactions in multiple sclerosis: disease specificity and relationship to circulating tumour necrosis factor-α and soluble adhesion molecules

Abstract

This study addressed two questions; first, whether the supranormal adherence of blood lymphocytes from patients with multiple sclerosis (MS) to endothelial cell monolayers treated with tumour necrosis factor-alpha (TNF alpha) was a feature common to other inflammatory disorders; and second, whether the adherence properties of blood lymphocytes from MS patients were related to changes in disease activity and to levels of circulating TNF alpha and soluble adhesion molecules. In the first part of the investigation, lymphocytes from 14 patients with MS were more adherent to TNF alpha-treated endothelial cells (P < 0.01) than those from healthy controls, whereas the adherence properties of lymphocytes from 12 patients with rheumatoid arthritis, eight patients with psoriasis and ten patients with neurological diseases other than MS were normal. In the second phase of the work, measurement of the adhesive properties of lymphocytes isolated at monthly intervals from a further six MS patients over a 5-8 month period, found that changes in binding to TNF alpha-treated endothelial cells, directly paralleled changes in circulating levels of TNF alpha (r = 0.77; P < 0.001) and soluble vascular cell adhesion molecule-I (sVCAM-1) r = 0.67; P = 0.001). An increase in disease activity, measured by T2-weighted and gadolinium-enhanced magnetic resonance imaging of the central nervous system (CNS), occurred in two patients and was associated with heightened lymphocyte adhesiveness and a rise in serum TNF alpha levels. Further analysis of the 34 serum samples from the six MS patients revealed a direct relationship between the concentration of sL-selectin and soluble intercellular adhesion molecule-I (sICAM-I) (r = 0.65; P < 0.001) and between sL-selectin and sTNF alpha (r = 0.42; P < 0.02). These findings support the view that disease activity in MS is associated with an increased adhesive interaction of blood lymphocytes with vascular endothelium at inflammatory sites within the CNS.

CD47-dependent immunomodulatory and angiogenic activities of extracellular vesicles produced by T cells

“…Cross talk between endothelial cells and T lymphocytes in normal physiological as well as pathological conditions has been well established ( Vora et al, 1997 ; Choi et al, 2004 ). Our data demonstrate that T cell derived EVs can alter endothelial VEGF signaling, tube formation, and gene expression.…”

Increased Neutrophil Adherence in Psoriasis: Role of the Human Endothelial Cell Receptor Thy-1 (CD90)

“…Several studies examined the adhe-sion of MNCs to psoriatic skin, especially to the dermal vascular endothelium (Chin et al, 1990a, b;Cai et al, 1996). MNCs from psoriatic patients bind more avidly to activated ECs than to non-activated EC (LeRoy et al, 1991;Dunky et al, 1997;Vora et al, 1997). In contrast, only few data exist on the adhesion of psoriatic PMNCs, which are also very prominent in psoriatic skin lesions and are thought to be responsible for many important features of the disease (Schö n et al, 2000;Terui et al, 2000;Toichi et al, 2000).…”

Determination of soluble ICAM-1 and TNFalphaR in the cerebrospinal fluid and serum levels in a population of Brazilian patients with relapsing-remitting multiple sclerosis

“…Indeed constitutive adhesion molecules expressed or induced during active immune response, can be released from cerebral endothelial cell membranes following cytokine stimulation 14,15 . Moreover soluble TNF receptors (sTNF-R) capable of antagonize TNF action in vivo also up regulate TNF-α levels thus inducing TNF-associated activities 10,11,17,18 , such as cytotoxicity. Furthermore, the potential contribution of TNFα to tissue injury within the CNS 2 is also dependent upon activation of CD95, a signaling receptor member of the TNF-R superfamily expressed on the target cells (e.g oligodendrocytes).…”

“…integrins: LFA-1; CD11a/CD18) influenced by locally produced cytokines [5][6][7] . A circulating soluble form of ICAM (sICAM-1) released mainly by CNS microvascular endothelial cells, has been detected in the serum of normal individuals 8 although high levels have been associated with pathological conditions [9][10][11] . The sICAM-1 influence transendothelial migration of leukocyte across inflamed BBB 12 and thus may be a useful indicator of inflammatory disease and integrity of the BBB 12,13 .…”