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 war 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 ac utely injured by intravenous OA manifest increased levels of ICAM-1 wi thin 30-60 min. This study shows that human. umbilical vein endothelia l cells (HUVEC) can be wed in a bioassay to reveal some of the adhesio n molecule stimulating activities present in bronchoalveolar lavage fl uid (BALF) from post-OA-injected rats: (1) There is an as yet unidenti fied 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 measur able tumor necrosis factor-alpha (TNF alpha in 15 min BALF (BALF15). ( 2) BALF15 also stimulates cultured macrophage derived from BALF of nor mal 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 T NF 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 war equal to that of B ALF60 containing equivalent concentrations of TNF alpha. The ELAM indu cing activity of pure TNF alpha, however, was about 1/2 that of BALF60 containing equivalent concentrations of TNF alpha. The time courses f or ICAM and ELAM stimulation with pure TNF alpha or BALF60 containing equivalent levels of TNF alpha. were the same. The identity of the med iators in BALF15 and BALF60 that are not TNF alpha and the mechanisms by which OA injection stimulates cytokine production remain to be eluc idated.