Integrin-mediated intracellular Ca2+ signaling in Jurkat T lymphocytes.

Abstract

T lymphocytes interact with components of the extracellular matrix after transendothelial migration on their way to sites of inflammation. To characterize the molecular basis of the interaction between T lymphocytes with different extracellular matrix proteins, we investigated the role of intracellular Ca2+ as a signal mediating such interactions and identified the cell surface integrins involved in this process. When Jurkat T lymphocytes loaded with the calcium-sensitive fluorescent dye fura-2 were placed on coverslips coated with human fibronectin, human collagen types I, IV, and VI, human tenascin, human laminin I, or mouse laminin I, an elevation in intracellular Ca2+ concentration was observed. In contrast, contact of the Jurkat T lymphocytes with vitronectin and thrombospondin did not induce Ca2+ signals in more cells as compared with control measurements in which cells were in contact with only BSA or polylysine. Furthermore, the percentage of Jurkat T lymphocytes responding with Ca2+ signals to collagen types I and IV, fibronectin, and laminin I was completely reduced to levels observed on BSA or polylysine when the cells were pretreated with specific anti-integrin Abs, suggesting a role for cell surface integrins as mediators of cell matrix-induced intracellular Ca2+ signaling. Similar results were obtained with peripheral human T lymphocytes activated by phytohemagglutinin.

Adhesion to laminin-1 and collagen IV induces the formation of Ca 2+ microdomains that sensitize mouse T cells for activation

“…1, D, E, and G, and 2, D, E, G, and H). In contrast, Jurkat T cells respond with an increase in global [Ca 2+ ] i when acutely placed on the human or mouse forms of various ECM proteins ( 8 , 11 ). This discrepancy may be due to the blast-like activated T cell nature of Jurkat T cells in which integrin signaling produces sufficient Ca 2+ -mobilizing second messengers to evoke global Ca 2+ signaling.…”

“…In Jurkat T cells, integrin-mediated adhesion to ECM proteins triggers an increase in global free cytosolic calcium (Ca 2+ ) concentration ([Ca 2+ ] i ) ( 8 ). Upon binding of integrins to ECM proteins, phosphorylation of focal adhesion kinase (FAK) and subsequent activation of phospholipase C–γ (PLC-γ) ( 9 ) occurs.…”

T cell Ca2+ microdomains through the lens of computational modeling

“…Long before the observation of ADCM, Weissmann and colleagues described global Ca 2+ responses in Jurkat T cells that were triggered by integrin-mediated adhesion to extracellular matrix (ECM) proteins ( 29 ). These Ca 2+ signals were dependent on the phosphorylation of focal adhesion kinase (FAK).…”