Sequential appearance of inflammatory mediators in rat bronchoalveolar lavage fluid after oleic acid-induced lung injury.
The oleic acid (OA) model of rat lung injury was originally developed as a model of fat embolism syndrome. A single intravenous dose of pure OA causes an acute diffuse lung injury, which, in its initial stages, histologically and physiologically resembles human ARDS. Rat lungs acutely injured by intravenous OA manifest increased levels of ICAM-1 within 30-60 min. This study shows that human umbilical vein endothelial cells (HUVEC) can be used in a bioassay to reveal some of the adhesion molecule stimulating activities present in bronchoalveolar lavage fluid (BALF) from post-OA-injected rats: (1) There is an as yet unidentified ICAM-1 and ELAM (E Selectin) inducing activity in BALF within 15 min of OA injection that is not TNF alpha; there is very little measurable tumor necrosis factor-alpha (TNF alpha) in 15 min BALF (BALF15). (2) BALF15 also stimulates cultured macrophage derived from BALF of normal rat lungs to produce TNF alpha. (3) By 60 min after OA injection, 50-75% of the ICAM-1 and ELAM inducing activity in BALF (BALF60) is TNF alpha; BALF60 contains about 250-280 pg/mL TNF alpha. The other 25-50% adhesion molecule-inducing activity in BALF60 is unidentified. (4) The ICAM-1-inducing activity of pure TNF alpha was equal to that of BALF60 containing equivalent concentrations of TNF alpha. The ELAM inducing activity of pure TNF alpha, however, was about 1/2 that of BALF60 containing equivalent concentrations of TNF alpha. The time courses for ICAM and ELAM stimulation with pure TNF alpha or BALF60 containing equivalent levels of TNF alpha were the same. The identity of the mediators in BALF15 and BALF60 that are not TNF alpha and the mechanisms by which OA injection stimulates cytokine production remain to be elucidated.
Syrbu
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Department of Pharmacology, University of Connecticut Health Center, Farmington, USA.
Thrall
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Smilowitz
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HM
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D019040:E-Selectin / Q000096:biosynthesis; D018836:Inflammation Mediators / Q000032:analysis*; D007275:Injections, Intravenous; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D008171:Lung Diseases / Q000139:chemically induced* / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D019301:Oleic Acid; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology
D019040:E-Selectin; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D019301:Oleic Acid