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 endotoxin (5 micrograms/kg) with chronic lung lymph fistula (n = 15), we measured the changes in glucocorticoid receptor (GCR) binding capacity in lung tissue by means of radioligand binding assay. The content of cortisol and the activity of phospholipase A2 (PLA2) were also measured. The results showed that the maximal binding capacity (Bmax) of GCR in lung cytoplasma decreased continuously 2 h (113 +/- 3 versus 66 +/- 2 fmol/mg protein, p < 0.01), 4 h (105 +/- 6 versus 52 +/- 3 fmol/mg protein, 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 elevated at 0.5 h and remained at a high level until 4 h after the infusion. 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 was 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 lung injury. The glucocorticoid hypofunction caused by reduced GCR binding capacity may accelerate the pathologic response of acute lung injury.(ABSTRACT TRUNCATED AT 250 WORDS)
Liu
L Y
LY
Department of Respiration, Xijing Hospital, Fourth Military Medical University, Xian, People's Republic of China.
Sun
B
B
Tian
Y
Y
Lu
B Z
BZ
Wang
J
J
D000818:Animals; D002908:Chronic Disease; D003600:Cytosol / Q000737:chemistry / Q000378:metabolism; D004195:Disease Models, Animal; D004731:Endotoxins / Q000633:toxicity*; D004926:Escherichia coli; D005260:Female; D005402:Fistula / Q000378:metabolism; D006854:Hydrocortisone / Q000097:blood; D008168:Lung / Q000737:chemistry / Q000378:metabolism*; D008206:Lymphatic Diseases / Q000378:metabolism; D010741:Phospholipases A / Q000032:analysis / Q000378:metabolism*; D054467:Phospholipases A2; D011869:Radioligand Assay; D011965:Receptors, Glucocorticoid / Q000032:analysis / Q000378:metabolism*; D012128:Respiratory Distress Syndrome / Q000139:chemically induced* / Q000378:metabolism*; D012756:Sheep; D013997:Time Factors
D004731:Endotoxins; D011965:Receptors, Glucocorticoid; D010741:Phospholipases A; D054467:Phospholipases A2; D006854:Hydrocortisone