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Blocking platelet-neutrophil aggregates may reverse lung injury
Antiplatelet agents and thromboxane receptor antagonists are possible treatment options.
Therapy to inhibit platelet neutrophil aggregates and/or neutralize platelet derived proinflammatory mediators may provide a novel therapeutic approach to acute lung injury that should be explored in further clinical trials, according to a recent study.
“Leukocytes get activated in inflammation and can stick together with platelets. This then creates a very powerful adhesive compound that essentially makes the adhesion of leukocytes and platelets much more efficient and causes damage to the endothelial cell,” Klaus Ley, MD, director of the Robert B. Berne Cardiovascular Research Center at the University of Virginia Health System, said in an interview.
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Ley said agents like thromboxane receptor antagonists or antiplatelet drugs could be therapeutic options for acute lung injury.
Gregory Vercellotti, MD, professor of medicine at the University of Minnesota Medical School and section editor of Hem/Onc Today’s Vascular Disorders section, said glycoprotein IIbIIIa inhibitors could possibly play a role, but clinicians would have to be aware of an increased risk for bleeding.
For the current study, Ley and colleagues investigated the role of platelet–neutrophil interactions in a murine model of acid-induced lung injury.
According to the research abstract, the acid aspiration induced P-selectin–dependent platelet neutrophil interactions in the blood and lung capillaries. Reducing circulating platelets or blocking P-selectin halted the development of acute lung injury.
When researchers analyzed bone marrow chimeras, they determined that platelet, not endothelial, P-selectin was responsible for the injury. The interaction of platelets with neutrophils and endothelia was associated with thromboxane A2 formation, with detrimental effects on permeability and tissue function. Activated platelets induced endothelial expression of intercellular adhesion molecule 1 and increased neutrophil adhesion. According to the researchers, inhibition of platelet-neutrophil aggregation improved gas exchange, reduced neutrophil recruitment and permeability, and prolonged survival.
Vercellotti said this data expanded previous knowledge by focusing on the role of platelets and the induction of P-selectin. Further research should focus on the role that gastric acid can play in activating complement, he said. – by Jeremy Moore
For more information:
- Zarbock A, Singbartl K, Ley K. Complete reversal of acid-induced acute lung injury by blocking of platelet-neutrophil aggregation. J Clin Invest. 2006;116:3211-3219.