Selectins revisited: the emerging role of platelets in inflammatory lung disease

Abstract

Neutrophil infiltration into the lung is considered a crucial step in the pathogenesis of acute lung injury, yet data on the underlying mechanisms have been ambiguous: although selectin-mediated leukocyte rolling is absent in lung capillaries, therapeutic strategies targeted at selectin-mediated cell-cell interactions yield partial protection. The study by Zarbock and coworkers in this issue of the JCI solves this apparent contradiction by identifying selectin-mediated platelet-neutrophil interaction as a critical step in the mutual activation of leukocytes and endothelial cells (see the related article beginning on page 3211). The emerging role of platelets may be of broad clinical relevance in lung inflammatory disorders, including asthma, chronic obstructive pulmonary disease, and cystic fibrosis.

Figure 1. Scheme for the role of platelets in the recruitment of neutrophils to the lung.

Initial P-selectin–dependent interaction of neutrophils with platelets, possibly in conjunction with platelet-endothelial interactions (left), results in mutual cell activation and release of the pro-inflammatory eicosanoid TXA₂ (right). Subsequent activation of endothelial TXA₂ receptors (TP) induces de novo expression of ICAM-1, resulting in firm neutrophil adherence via β₂-integrins.