Volumen: 17 # Number : 1
Publication Date : Enero - Abril Year: 2013
Authors: Etulain J1, Carestia A1, Rivadeneyra L1, Fondevila C2, Schattner M1
Abstract: Acidosis is one of the hallmarks of the inflammatory
microenvironment present in situations of vascular
injury, tumor, atherosclerosis and inflammatory lung diseases. In addition to its key role in hemostasis and thrombosis, platelets also play an important role in these pathologies. Our previous studies showed that acidosis dampens platelet haemostatic functions, and promotes inflammatory responses mediated by P-selectin expressed on the platelet surface. In this study we examined the molecular mechanisms involved
in these processes. While phosphorylation of some molecules involved in platelet activation (Src, Akt y ERK) was significantly inhibited by acidosis, the activation of p38 or NFκB was not modified or even increased respectively, with the decrease in pH. The increased expression of P-selectin observed in acidosis remained in the presence of inhibitors of Src (PP1), PI3K/Akt (Ly294002), and ERK (U0126). In addition,
this phenomenon was not modified by platelets incubation with blockers of p38 (SB203580) and NFκB (Ro1069920), but decreased significantly in the simultaneous
presence of both inhibitors. Accordingly with the augmented P-selectin expression, the formation of platelet-leukocyte aggregates, as well as leukocyte migration in the presence of platelets, were increased by acidosis and both cellular processes were reversed by the combined presence of SB203580 or Ro1069920. Together, these results indicate that inflammatory responses mediated by platelet in acidic conditions require simultaneous activation of p38 and NFκB, and raise the possibility of new therapeutic targets for the treatment of inflammation.
Key words: platelets, p-selectin, inflammation, acidosis
Trabajo premiado con Mención Especial en el
X Congreso Argentino de Hemostasia y Trombosis
Pages : 15-20
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