Role of eicosanoids in staphylococcal alpha-toxin-induced lung injury in the rat.

Abstract

We investigated the role of arachidonic acid-derived eicosanoids in staphylococcal alpha-toxin (alpha-T)-induced lung injury. Bolus injection of 200 and 500 micrograms alpha-T into isolated perfused rat lungs resulted in increased pulmonary perfusion pressure followed by lung weight gain. Inhibition of pressure change with papaverine (10(-4) M) failed to abolish lung edema. Furthermore, alpha-T increased the permeability-surface area product in papaverine-treated lungs and caused marked endothelial cell injury and interstitial edema as documented by electron microscopy. alpha-T dose dependently increased lung tissue thromboxane B2 (TxB2) levels and leukotriene C4 levels. In lungs given 0, 200, and 500 micrograms of alpha-T, TxB2 (in micrograms/g wet lung) values were 16.3 +/- 2.8, 25.0 +/- 3.0, and 54.2 +/- 6.2; and leukotriene C4 values were 4.6 +/- 1.1, 6.7 +/- 1.2, and 22.1 +/- 3.8, respectively. Inhibition of cyclooxygenase enzyme with indomethacin (10(-5) M) or lipoxygenase enzyme with 2(12-hydroxydodeca-5,10-dinyl)-3,5,6-trimethyl-1,4-benzoq uin one (AA861, 10(-5) M) attenuated the vasoconstriction and prevented lung edema due to low dose (200 micrograms) but not high dose (500 micrograms) alpha-T. The protective effect of these inhibitors on lung edema is in part due to decreases in alpha-T-stimulated venoconstriction because alpha-T-induced increase in lung microvascular pressure was attenuated by indomethacin and AA861 pretreatment. We conclude that both eicosanoid-dependent and eicosanoid-independent mechanisms contribute to alpha-T-induced lung edema in the rat.

• Authors: S W Chang, J Czartolomna, N F Voelkel
• Journal: The American journal of physiology (Am J Physiol) Vol. 262 Issue 4 Pt 1 Pg. L502-10 (Apr 1992) ISSN: 0002-9513 [Print] United States
• PMID: 1566864 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Bacterial Toxins
• Eicosanoids
• Hemolysin Proteins
• staphylococcal alpha-toxin

Topics

• Animals
• Bacterial Toxins (pharmacology)
• Blood Pressure (drug effects)
• Eicosanoids (analysis, physiology)
• Hemolysin Proteins
• Lung (drug effects, pathology, ultrastructure)
• Male
• Microscopy, Electron
• Pulmonary Circulation (drug effects)
• Pulmonary Edema (chemically induced, prevention & control)
• Rats
• Rats, Inbred Strains
• Staphylococcus