Leukotriene B4 synthesis and neutrophil chemotaxis in chronic granulocytic leukaemia

Abstract

A sensitive gas chromatography-mass spectrometric method was used to measure the generation in whole blood of leukotriene B4 (LTB 4), a potent stimulator of neutrophil Chemotaxis, in eight patients with chronic granulocytic leukaemia (CGL) and 12 healthy controls. LTB 4 was detectable in unstimulated samples from all the patients (mean 194 (70 SEM) pg/ml), and the capacity for LTB4 production after stimulation with calcium ionophore (A23187) was similar in patients (32·1 (11) ng/106 leucocytes) and controls (38·1 (4) ng/10 6 leucocytes). In response to stimuli which induce neutrophil activation, LTB4 production was significantly greater in the patients than in controls: 35·6 (13) V 13·0 (3) ng/ml, p < 0·05 (f-met-leu-phe); and 42·4 (16) v 14·7 (4) ng/ml, p < 0·02 (opsonised zymosan). Anti-IgE stimulated considerably more LTB 4 production in patients with CGL than in controls (3·86(1·6) v 0·83 (0·43) ng/ml; p < 0·005) and this correlated significantly (p < 0·05) with the basophil count. Neutrophil Chemotaxis to LTB4, however, was significantly impaired in the patients with CGL even at the highest concentration of LTB4 (10-5 M). Chemotaxis to f-met-leu-phe, phagocytosis, and bacterial killing were normal. Thus although LTB4 synthesis is normal or even enhanced in patients with CGL, specific defects in LTB4-mediated responses may contribute to neutrophil dysfunction in this disease.