Mechanisms of the adult respiratory distress syndrome: selectins.

Abstract

The acute lung injury of adult respiratory distress syndrome (ARDS) is characterised by inflammatory cell accumulation and activation in the lung. Selectins are a family of adhesion molecules implicated in leucocyte-endothelial adhesion, whose receptors can exist in a cleaved, soluble form. We investigated whether circulating soluble selectin adhesion molecules, obtained from ARDS at-risk patients, were associated with subsequent ARDS development Eighty two patients, at risk of ARDS, were enrolled from three well-defined groups (multiple trauma, pancreatitis, perforated bowel). Plasma samples were obtained on hospital presentation and soluble L, E, and P selectins were quantified with a sandwich enzyme-linked immunosorbent assay (ELISA). Fourteen patients subsequently developed ARDS. Initial plasma soluble L-selectin (sL-selectin) levels were significantly lower in patients who progressed to ARDS compared to those who did not (p = 0*0001; 95% Cl for mean in ARDS patients as percent of that in non-ARDS patients, 27-61%). Moreover concentrations were lower than in 62 normal volunteers (range 0-37-6*55, median 1 83 ugImL, n = 62), suggesting that a selective reduction of sL-selectin correlates with susceptibility. In addition, a significant correlation was found between low values of sL-selectin and indices of subsequent lung injury including requirement for ventilation (p = 0*0001) and degree of respiratory failure (p=0.0001). A significant correlation was also found between low values of sL-selectin and patient mortality (p = 0*002). These results elucidate the inflammatory cell endothelial interactions in the early stages of ARDS and may be of prognostic value. (Lancet 1994;344:215-9) Early in the course of the adult respiratory distress syndrome (ARDS) -that is, one or two days after the manifestation of respiratory failure -the lung parenchyma is not significantly abnormal and the predominant histological findings are pulmonary oedema and accumulation of polymorphonuclear leucocytes (PMNs) in the pulmonary circulation, interstitium, and alveolar spaces.' The current paradigm by which PMNs are thought to migrate across the vascular endothelial barrier is a multistage process which begins with a loose attachment of endothelial or cell surface molecules (selectins) to receptors on PMNs or on the endothelium resulting in the phenomenon known as PMN "rolling".6 This is followed by a more firm adherence between other cell adhesion molecules (integrins) and their specific ligands that is triggered by various factors including interleukin (IL)-8, platelet activating factor, bacterial wall components, complement products, and, possibly, E (endothelial)-selectin.7-9 Recently, platelet endothelial adhesion molecule (PECAM)-1, another cell adhesion molecule from the immunoglobulin superfamily, has also been linked to PMN transmigration.' 01 Donnelly et all2 have recently measured circulating selectin fragments in the blood of patients at risk for ARDS and found that the level of soluble L-selectin was lower in those ...