These findings suggest that blocking the interaction between ‘primed’ platelets and neutrophils could reduce the risk of DVT. This genetic mutation caused SLC44A2 to interact with ‘primed’ platelets more weakly, which may explain why people with this genetic variant are protected from getting DVT. studied a genetic variant of the SLC44A2 protein which is found in 22% of people and is associated with a lower risk of developing DVT. Once the neutrophils interacted with the ‘primed’ platelets, they started making traps which increased the size of the blood clot by capturing other blood cells and proteins.įinally, Constantinescu-Bercu et al. Further experiments showed that integrin α IIbβ 3 binds to a protein on the surface of neutrophils called SLC44A2. This revealed that VWF ‘primes’ the platelets to interact with neutrophils via a protein called integrin α IIbβ 3. used a device that mimics the flow of blood to study how human platelets change when they are exposed to VWF. To answer this question, Constantinescu-Bercu et al.

However, it remained unclear how these recruited platelets interact with neutrophils and whether this promotes the onset of DVT. Platelets are recruited to the wall of the vein by a protein called “von Willebrand Factor” (or VWF for short). In addition to platelets, the pathological (or dangerous) clots that cause DVT also contain immune cells called neutrophils which fight off bacterial infections. Although certain inherited factors have been linked to DVT, the underlying mechanisms of the disease remain poorly understood. Developing such clots – also known as deep vein thrombosis (or DVT for short) – is one of the most common cardiovascular diseases and a major cause of death. Blood clots can also occur in places where they are not needed, such as deep veins in our legs or other regions of the body. Platelets in our blood form clots over sites of injury to stop us from bleeding. Taken together, these data reveal a previously unreported mode of platelet-neutrophil crosstalk, mechanosensitive NET production, and provide mechanistic insight into the protective effect of the SLC44A2 rs2288904-A polymorphism in venous thrombosis. This was confirmed using neutrophils homozygous for the SLC44A2 R154Q polymorphism. A polymorphism in SLC44A2 (rs2288904-A) present in 22% of the population causes an R154Q substitution in an extracellular loop of SLC44A2 that is protective against venous thrombosis results in severely impaired binding to both activated α IIbβ 3 and VWF-primed platelets. Binding of platelet α IIbβ 3 to SLC44A2 on neutrophils leads to mechanosensitive-dependent production of highly prothrombotic neutrophil extracellular traps. Here we report that, under flow, von Willebrand factor/glycoprotein Ibα-dependent platelet ‘priming’ induces integrin α IIbβ 3 activation that, in turn, mediates neutrophil and T-cell binding. Platelet-neutrophil interactions are important for innate immunity, but also contribute to the pathogenesis of deep vein thrombosis, myocardial infarction and stroke. A polymorphism in SLC44A2 (rs2288904-A) present in 22% of the population causes an R154Q substitution in an extracellular loop of SLC44A2 that is protective against venous thrombosis results in severely impaired binding to both activated αIIbβ3 and VWF-primed platelets. Binding of platelet αIIbβ3 to SLC44A2 on neutrophils leads to mechanosensitive-dependent production of highly prothrombotic neutrophil extracellular traps. Here we report that, under flow, von Willebrand factor/glycoprotein Ibα-dependent platelet 'priming' induces integrin αIIbβ3 activation that, in turn, mediates neutrophil and T-cell binding.

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