Acidosis downregulates platelet haemostatic functions and promotes neutrophil proinflammatory responses mediated by platelets

Thrombosis and Haemostasis - Tập 107 Số 01 - Trang 99-110 - 2012
Julia Etulain1, Soledad Negrotto, Agostina Carestia, Roberto Gabriel Pozner, María Albertina Romaniuk, Lina Paola D’Atri, Giannoula Klement, Mirta Schattner
1Thrombosis I Laboratory, National Academy of Medicine, CONICET, Buenos Aires, Argentina.

Tóm tắt

SummaryAcidosis 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-induced 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.

Từ khóa


Tài liệu tham khảo

10.1023/A:1008986329267

10.2741/3616

10.1016/j.cell.2004.09.004

Lim, 2007, Acta Med Indones, 39, 145

10.1016/j.jaci.2003.12.034

10.1016/S0049-3848(01)00374-7

Patscheke, 1981, Haemostasis, 10, 14

Rogers, 1972, Proc Soc Exp Biol Med, 139, 1100, 10.3181/00379727-139-36307

10.1016/0049-3848(83)90046-4

10.1042/BJ20100538

10.1111/j.1538-7836.2011.04394.x

10.1083/jcb.200112113

10.1096/fj.07-9524com

10.1124/jpet.106.109389

10.1172/JCI5191

10.1007/s11022-004-8228-3

10.1182/blood-2004-04-1257

10.1016/S0960-9822(01)00565-6

10.1083/jcb.200703185

Munnix, 2009, Thromb Haemost, 102, 1149, 10.1160/TH09-05-0289

Sinauridze, 2007, Thromb Haemost, 97, 425, 10.1160/TH06-06-0313

Nurden, 2008, Front Biosci, 13, 3532

10.1161/01.ATV.0000166521.90532.44

10.1182/blood-2007-09-113837

10.1182/blood-2011-01-330910

10.1073/pnas.0406682102

10.1182/blood-2002-12-3882

10.1152/ajpheart.00491.2010

Trevani, 1999, J Immunol, 162, 4849, 10.4049/jimmunol.162.8.4849

Brunetti, 2000, Thromb Haemost, 84, 478, 10.1055/s-0037-1614048

Andonegui, 1997, J Immunol, 158, 3372, 10.4049/jimmunol.158.7.3372

10.2741/3384

10.1083/jcb.105.4.1761

10.1016/0090-6980(81)90228-8

10.1182/blood-2010-02-268680

10.1016/j.jcf.2009.12.004

10.1111/j.1538-7836.2004.01009.x

10.1074/jbc.M809235200

10.1158/0008-5472.CAN-09-1370

Thông tin
Thông tin xuất bản

Thrombosis and Haemostasis

Tập 107 Số 01

99-110

Thông tin tác giả