CHANGES OF PULMONARY GLUCOCORTICOID RECEPTOR AND PHOSPHOLIPASE-A2 IN SHEEP WITH ACUTE LUNG INJURY AFTER HIGH-DOSE ENDOTOXIN INFUSION

In a sheep model of acute lung injury induced by an Escherichia coli e ndotoxin (5 mug/kg) with chronic lung lymph fistula (n = 15), we measu red the changes in glucocorticoid receptor (GCR) binding capacity in l ung tissue by means of radioligand binding assay. The content of corti sol and the activity of phospholipase A2 (PLA2) were also measured. Th e results showed that the maximal binding capacity (Bmax) of GCR in lu ng cytoplasma decreased continuously 2 h (113 +/- 3 versus 66 +/- 2 fm ol/mg protein, p < 0.01), 4 h (105 +/- 6 versus 52 +/- 3 fmol/mg prote in, p < 0.01), and 6 h (105 +/- 5 versus 37 +/- 2 fmol/mg protein, p < 0.01) after endotoxin infusion. Its affinity decreased markedly (p < 0.05) at 6 h after the infusion. The contents of cortisol in plasma el evated at 0.5 h and remained at a high level until 4 h after the infus ion. PLA2 activity rose from 97 +/- 25 to 188 +/- 12 U (p < 0.05), 99 +/- 13 to 285 +/- 25 U (p < 0.01), and 106 +/- 14 to 354 +/- 32 U (p < 0.01) at 2, 4, and 6 h after endotoxin infusion, respectively There w as a negative correlation between the Bmax of GCR and PLA2 activity (r = -0.87, p < 0.01). The findings indicate that there was a secondary GCR abnormality and a higher PLA2 activity during endotoxin-induced lu ng injury. The glucocorticoid hypofunction caused by reduced GCR bindi ng capacity may accelerate the pathologic response of acute lung injur y. Therefore, in the early phase of ARDS, administration of a GCR prot ector or PLA2 inhibitor may be beneficial.