Table 3.

Some Outstanding Questions Regarding Platelets, Megakaryocytes, Acute Lung Injury, and Acute Respiratory Distress Syndrome

• What are the biologic signals and factors that regulate platelet number, production, survival, and distribution in ALI and ARDS?

• What is the role of the lung in regulating thrombopoiesis in ALI, ARDS, and other critical illnesses?

• Do lung and marrow megakaryocytes have inflammatory and hemostatic activities in ALI, ARDS, and critical illness that complement their activities as thrombopoietic precursors?

• What are the functional characteristics of circulating platelets in common (pneumonia, sepsis, aspiration, trauma) and uncommon (MA-ARDS, others) subphenotypes of ARDS and animal models of these subphenotypes?

• Do functional characteristics (transcriptome, proteome, synthetic capacity, surface phenotype) of platelets change during the natural history of ALI and ARDS?

• What are the differences in function of circulating platelets and platelets sequestered in microvessels in the lungs in ALI and ARDS?

• What activities do platelets have in lung interstitial and intraalveolar compartments in ALI and ARDS?

• What are the precise mechanisms by which platelets regulate alveolar–capillary barrier integrity in ALI and ARDS? Do platelets regulate lymphatic barrier activity in these syndromes?

• What are the pivotal molecular consequences of platelet–leukocyte interactions in common and uncommon subphenotypes of ARDS?

• Do platelets have critical interactions with endogenous or therapeutically delivered stem cells or other reparative cell populations in lung injury?

• Can “adversary” functions of platelets be therapeutically targeted while preserving key “amicus” functions that are critical for lung defense and repair in ARDS?

• What tools can be developed (e.g., imaging methodologies, “in vivo cell biology assays”) to aid in posing and answering these questions in clinically meaningful ways?

Definition of abbreviations: ALI = acute lung injury; ARDS = acute respiratory distress syndrome; MA-ARDS = malaria-associated acute respiratory distress syndrome.