Amicus or Adversary Revisited: Platelets in Acute Lung Injury and Acute Respiratory Distress Syndrome

Abstract

Platelets are essential cellular effectors of hemostasis and contribute to disease as circulating effectors of pathologic thrombosis. These are their most widely known biologic activities. Nevertheless, recent observations demonstrate that platelets have a much more intricate repertoire beyond these traditional functions and that they are specialized for contributions to vascular barrier integrity, organ repair, antimicrobial host defense, inflammation, and activities across the immune continuum. Paradoxically, on the basis of clinical investigations and animal models of disease, some of these newly discovered activities of platelets appear to contribute to tissue injury. Studies in the last decade indicate unique interactions of platelets and their precursor, the megakaryocyte, in the lung and implicate platelets as essential effectors in experimental acute lung injury and clinical acute respiratory distress syndrome. Additional discoveries derived from evolving work will be required to precisely define the contributions of platelets to complex subphenotypes of acute lung injury and to determine if these remarkable and versatile blood cells are therapeutic targets in acute respiratory distress syndrome.

The contribution of recipient platelets in TRALI: has the jury reached a verdict?

“…Several studies of experimental acute lung injury in settings other than TRALI do, however, appear to indicate a more essential role for PLTs as crucial effector cells, although further work is required to more accurately define their contributions. In line with this, it has been described in a murine study that PLTs may be produced in the lungs and that PLTs may also play an essential role in murine lung development through Clec‐2/podoplanin .…”

P2Y12 Inhibition beyond Thrombosis: Effects on Inflammation

“…To summarize, sepsis-induced organ dysfunctions result from the interplay between uncontrolled activation of the complement, coagulation, and inflammatory systems. Platelet-mediated inflammatory response is now recognized as a critical player in the pathophysiology of sepsis, and is especially involved in sepsis-induced experimental acute lung injury (ALI) and clinical life-threatening acute respiratory distress syndrome (ARDS) through several mechanisms, including pathogen sensing, release of inflammatory mediators, recruitment and activation of immune cells and thrombosis [109,[147][148][149][150][151].…”

Novel mechanisms regulating endothelial barrier function in the pulmonary microcirculation

“…New cellular players such as platelets have received increasing attention for their non‐haemostatic influence on barrier integrity and immunological effector functions (for a detailed overview on the functions of platelets in ALI and ARDS refer to Middleton et al . ). Beside the bone marrow, the lung has recently been described as a haematopoietic organ that contributes significantly to the systemic platelet pool (Lefrancais et al .…”