|
  
- 积分
- 0
- 威望
- 0
- 包包
- 3465
|
Calcium fluctuations in the bottom layer of a platelet mass are propagated upwards to determine the size of a blood clot, or thrombus, according to results from Nesbitt et al. presented on page 1151.Platelets adhere to substrates in the vessel wall through receptors such as GPIb and certain integrins. Initial receptor engagement stimulates Ca2 spikes in the platelets that lead to firm, permanent adhesion between the vessel wall and the primary layer of platelets. Now, Nesbitt et al. show that Ca2 signals in this bottom layer are propagated among cells to promote platelet aggregation.
( b9 e: R y+ k* J( T9 h
; X; r4 F8 o# n$ Z/ VThe group visualized cytosolic Ca2 concentrations in platelets and found that cells with strong Ca2 oscillations efficiently nucleated platelet aggregates. Flowing platelets that contacted an anchored platelet at the peak of its Ca2 fluctuation adhered and initiated their own Ca2 oscillations. Propagation of the Ca2 signals, which the authors call intercellular calcium communication, requires integrin IIb?3 and ADP, as well as the ADP receptor, P2Y12. The group proposes that integrin activation tethers neighboring platelets, initiates Ca2 spikes through release of stores in the newly adherent platelet, and stimulates local release of ADP. ADP activation of P2Y12 signaling in nearby cells amplifies the Ca2 flux in the nearby cells and sustains integrin-driven aggregation. @* d( M. Q% r4 L1 z8 P$ C
/ Q% b8 }0 G) d e6 {2 h, s, \6 v7 ~The results provide a model to explain how the vessel substrate collagen, which only contacts the first layer of adhering platelets, is nonetheless particularly effective at promoting thrombus growth. The group shows that compared with von Willebrand factor (vWf), another vessel substrate, collagen induced both stronger and more widespread Ca2 oscillations in the primary layer of adhering platelets. As a result, collagen-based thrombi were over five times larger than those that formed on vWf.(Ca2 oscillations passed among platelets) |
|
发表于 2009-3-6 00:57
发表于 2015-5-31 17:43
