INVESTIGADORES
SCHATTNER Mirta Ana
artículos
Título:
Acidosis dials down platelet haemostatic functions and promotes neutrophil proinflammatory responses mediated by platelets.
Autor/es:
ETULAIN J; NEGROTTO S; CARESTIA A; POZNER R; ROMANIUK MA; D'ATRI LP; KLEMENT GL; SCHATTNER M
Revista:
THROMBOSIS AND HAEMOSTASIS
Editorial:
SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN
Referencias:
Año: 2012 vol. 107 p. 99 - 110
ISSN:
0340-6245
Resumen:
Acidosis is one of the hallmarks of tissue injury such as trauma, infection,
inflammation, and tumour growth. Although platelets participate
in the pathophysiology of all these processes, the impact of acidosis on
platelet biology has not been studied outside of the quality control of
laboratory aggregation assays or platelet transfusion optimization.
Herein, we evaluate the effect of physiologically relevant changes in
extracellular acidosis on the biological function of platelets, placing
particular emphasis on haemostatic and secretory functions. Platelet
haemostatic responses such as adhesion, spreading, activation of αIIbβ3
integrin, ATP release, aggregation, thromboxane B2 generation, clot retraction
and procoagulant activity including phosphatidilserine exposure
and microparticle formation, showed a statistically significant inhibition
of thrombin-induced changes at pH of 7.0 and 6.5 compared to
the physiological pH (7.4). The release of alpha granule content was differentially
regulated by acidosis. At low pH, thrombin or collagen-in-
Correspondence to:
Mirta Schattner
Academia Nacional de Medicina
Pacheco de Melo 3081
Buenos Aires (1425), Argentina
Tel.: +5411 4805 5759, Fax: +5411 4805 0712
E-mail: mschattner@hotmail.com
duced secretion of vascular endothelial growth factor and endostatin
were dramatically reduced. The release of von Willebrand factor and
stromal derived factor-1α followed a similar, albeit less dramatic pattern.
In contrast, the induction of CD40L was not changed by low pH,
and P-selectin exposure was significantly increased. While the generation
of mixed platelet-leukocyte aggregates and the increased chemotaxis
of neutrophils mediated by platelets were further augmented
under acidic conditions in a P-selectin dependent manner, the increased
neutrophil survival was independent of P-selectin expression. In conclusion,
our results indicate that extracellular acidosis downregulates
most of the haemostatic platelet functions, and promotes those involved
in amplifying the neutrophil-mediated inflammatory response.