PubMed · 5416209
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L M Sherwood. 1970-03-26. Magnesium ion and parathyroid function.. https://doi.org/10.1056/nejm197003262821315
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To understand the mechanism by which human red blood cells (RBCs) contribute to hemostasis and thrombosis, we have examined the effects of metabolites released by activated platelets on intact RBCs. Prostaglandin E2 (PGE2), a signal molecule produced by activated platelets, was observed to lower the filterability of human erythrocytes by approximately 30% at 10(-10) M. PGE2 also caused a reduction in mean cell volume of approximately 10%. The shrinkage of red cells after PGE2 treatment was confirmed by documenting a decrease in osmotic fragility and an increase in cell density following exposure to the hormone. Careful analysis, however, revealed that only approximately 15% of the erythrocytes responded to stimulation with PGE2. Examination of the cause of cell shrinkage showed that induction of a PGE2-stimulated K+ efflux pathway leading to rapid loss of cellular K+ was responsible. The PGE2-stimulated K+ loss was also observed to be Ca2+-dependent, suggesting the possible involvement of the Gardos channel. Gardos channel participation was supported by the observation that two Gardos channel inhibitors, charybdotoxin and clotrimazole, independently blocked the PGE2-stimulated K+ efflux. Further evidence for Gardos channel activation came from experiments aimed at characterizing the efflux pathway followed by the obligatory counterion. Thus, K+ efflux was readily stimulated even when NO3- was substituted for Cl-, suggesting that neither KCl cotransport nor Na/K/2Cl cotransport plays a prominent role in the PGE2-induced cell shrinkage. Further, the anion transporter band 3 was implicated as the counterion efflux route, since DIDS inhibited the PGE2-stimulated cell volume change without blocking the change in membrane potential. Taken together, we propose that release of PGE2 by activated platelets constitutes part of a mechanism by which activated platelets may recruit adjacent erythrocytes to assist in clot formation.
In T cells, cell surface expression of CD45, a transmembrane tyrosine phosphatase, is required for T cell receptor (TCR) signal transduction. Indirect evidence suggests that CD45 function in TCR signaling involves the dephosphorylation of the C-terminal negative regulatory site of p56(lck), Tyr-505. To evaluate the importance of CD45-mediated dephosphorylation of p56(lck) Tyr-505 in TCR signaling, we established CD45(-) Jurkat cell lines expressing various forms of a chimera containing the extracellular and transmembrane domains of the epidermal growth factor receptor (EGFR) fused to p56(lck). We report that an activated EGFR/Lck chimera is able to reconstitute a Ca2+ response after CD3 stimulation in the absence of CD45 expression. In addition, the wild-type and kinase inactive versions of the EGFR/Lck chimera fail to restore early signaling. Restoration of the response by EGFR/LckF505 required EGF binding to the chimeric kinase. Altogether, these results provide the first direct evidence that the lack of efficient dephosphorylation of p56(lck) Tyr-505 is, in part, responsible for the unresponsiveness of CD45(-) cells. They also indicate that a second event is required for p56(lck) function in TCR signaling in addition to its dephosphorylation at Tyr-505.
Our aim was to observe whether normal human T-cells respond to mitogenic stimulation with large whole-cell inward currents (composed of identifiable single-channel contributions) when [Ca2+]i is not markedly lowered but instead kept normal or moderately low, as has been reported in human leukaemic Jurkat T-cell line and T-cell clones [Kuno et al. (1986) Nature 323, 269-73; Kuno and Gardner (1987) Nature 326, 301-304; Gardner (1990) Annu. Rev. Immunol. 8, 231-252]. Whole-cell patch recordings showed no such currents in cells otherwise normally responding to depolarisation with the macroscopic IK described in T-lymphocytes and thus deemed viable, in agreement with the notion that Ca2+ influx in normal T-cells enterily depends on depletion of internal stores [Putney (1986) Cell Calcium 7, 1-12; Putney (1990) Cell Calcium 11, 611-624].