Studies on the mechanisms of granulocyte dysfunctions in severely burned patients--evidence for altered leukotriene generation

Abstract

The leukotriene generation (LTB4, 20-OH-LTB4, 20-COOH-LTB4) from PMNs of severely burned patients (n = 6) was studied by reversed-phase HPLC. Granulocytes from all patients showed a decrease in leukotriene generation which only returned to normal levels when the patients recovered from their injuries. The leukotriene generation induced by different stimuli, i.e., the Ca++-ionophore A23187 (7.3 microM) or opsonized zymosan (2 mg) in the presence of exogenous arachidonic acid (60 microM) showed similar stimulation profiles. The cellular differentiation of the respective granulocyte fractions revealed that the decreased leukotriene generation was accompanied by the occurrence of immature granulocytes in the peripheral blood. Furthermore, the studies in the presence of exogenous arachidonic acid showed that the defect in leukotriene generation from granulocytes of surviving patients was due to the availability of metabolizable substrate (i.e., free arachidonic acid). Granulocytes from one nonsurviving patient showed in addition a defect in the metabolic ability of arachidonic acid to generate the respective leukotrienes. The generation of reactive oxygen species did not correlate with the observed alterations in the formation of the leukotrienes.