sepsis has been classically considered the archetypal clinical condition with molecular links between inflammation and coagulation .
both inflammation and thrombosis can be orchestrated by the interactions between circulating cells , such as lymphocytes , platelets , and vascular cells , which under activation or apoptosis lead to the release of circulating microparticles ( mps ) . in the previous issue of critical care ,
prez - casal and colleagues hypothesized that circulating mps may retain their anti - inflammatory and cytoprotective properties in septic patients during recombinant human activated protein c ( rhapc ) infusion in vivo and probably participate in its clinical benefit .
the same group has previously shown that activated protein c ( apc ) can generate mps in vitro from endothelial cell protein c receptor ( epcr)-expressing cells , which retain anticoagulant and protease - activated receptor-1 ( par-1)-dependent anti - inflammatory properties .
apc binding to epcr at the endothelial cell surface and apc on mp - epcr could cleave and activate par-1 , sphingosine 1-phosphate receptor and kinase insert domain receptor .
rhapc treatment for severe sepsis can induce the generation and release of mps in vivo , with a clinical correlative trend towards improved outcome . circulating mps from patients during rhapc treatment express apc , epcr and cd13 .
these mps interact with endothelial cells and induce changes in gene expression to inhibit apoptosis and reduce endothelial permeability .
these effects require par-1 activation by apc in an epcr - bound conformation , confirming the evidence for the assembled epcr - apc complex on in vivo - derived mps .
the present work suggests that mps could disseminate apc function and activate endothelial par-1 at distal vascular sites .
the mps represent an additional circulatory form of apc receptor in human plasma , which is different from soluble epcr .
mp - associated apc is stable in measurable levels , and activities would point to physiological and clinical relevance as bioactive effectors in rhapc - treated patients and contribute to the effectiveness of rhapc in severe sepsis
the authors did not analyze the subpopulation of cd13 mps upon rhapc treatment , whether they are from endothelial or leukocyte origins .
indeed , they have shown that apc induces mp - associated epcr formation from monocytes and human endothelial cells .
furthermore , whether such mps contribute to the ability of rhapc treatment to improve cardiovascular function - including arterial contractility and endothelial dysfunction by decreasing tissue inflammation and oxidative stress as reported in an experimental model of sepsis   - remains to be determined .
a fragile balance between the harmful and helpful effects of mps especially during severe sepsis should be underlined .
circulating mps from septic patients might exert a protective role at the vascular level by compensating hyporeactivity , but they might also contribute to the cause of multiorgan failure in sepsis and induce deleterious protein changes in target tissues .
it would be of interest to test the hypothesis that rhapc via increased certain subtypes of mps bearing epcr / apc would contribute to the correction of multiple organ failure , which would lead to increased survival .
the clinical relevance of rhapc treatment via increased apc / epcr - mps requires further exploration , especially in larger numbers of patients with septic shock and higher mortality . in conclusion
mps could potentially be developed as new therapeutic tools to transfer biological vectors of cellular communication and are able to modulate important cellular regulatory functions at a distal site of its production in response to pharmacological agents such as rhapc .
apc : activated protein c ; epcr : endothelial protein c receptor ; mp : microparticle ; par-1 : protease - activated receptor-1 ; rhapc : recombinant human apc .
 activated protein c ( apc ) , a physiological coagulation inhibitor , has been shown to reduce mortality in patients with severe sepsis . 
 apc exerts pleiotropic cytoprotection by a mechanism that requires its interaction with endothelial cell protein c receptor and protease - activated receptor-1 on target cells . in the previous issue , 
 prez - casal and colleagues elegantly demonstrate that apc , using its recombinant form ( rhapc ) , can communicate to target cells through release of microparticles ( mps ) , small membrane vesicles released from activated cells , to induce anti - apoptotic and anti - inflammatory properties that might participate in the improvement of patient outcome . of interest is the fact that apc itself promotes the release of mps from target cells including endothelial cells and monocytes . 
 these mps bear the endothelial cell protein c receptor / apc molecules and can transfer the message to target cells including those of origin to induce cytoprotection . 
 the long - range apc signal can thus be mediated by mps in vivo upon pharmacological treatment using rhapc in severe septic patients . a novel pharmacological approach targeting mp production and properties 
 could therefore be used to treat severe sepsis in addition to other well - known actions of apc via direct interaction with the cells of interest . 