The effect of vitamin E on rabbit neutrophil activation.

Chemoattractants such as N-formylmethionyl leucyl phenylalanine (FMLP) cause neutropenia in vivo. The sequestered neutrophils may block the microvasculature and contribute to respiratory distress. Neutrophils from humans receiving 1600 units vitamin E per day have reduced oxidative activity. To test whether vitamin E attenuates the responses of neutrophils to FMLP in vivo we gave rabbits four daily intramuscular injections of 100 mg vitamin E. Serum levels of the vitamin were 2.34 +/- 0.15 mg% compared to 0.19 +/- 0.04 mg% in control rabbits receiving placebo injections. On the fifth day testing was done before and after injecting FMLP. Variables monitored were the absolute granulocyte count (AGC), systolic, diastolic and mean blood pressures (MBP), heart rate, PO2, PCO2, pH and respiratory rate. When 0.5 microgram FMLP was injected intravenously the AGC decreased (at 2.5 min the percentage change was -89.7 +/- 8.0 with vitamin E and -97.0 +/- 2.7 without vitamin E; P = 0.2). MBP decreased also (% change, -29.0 +/- 13.0 with vitamin E and -36.3 +/- 16.0, without vitamin E). By 15 min recovery was seen (AGC % change, -26.0 +/- 17 with vitamin E and -78.7 +/- 10.5, without vitamin E; P = 0.01; MBP % change, -9.3 +/- 3.8 with vitamin E and -52.3 +/- 10.1 without vitamin E). Chromatographic analysis of serum extracts revealed increases in 6-keto-PGF1 alpha after stimulation. Studies with [3h]thymidine-labelled neutrophils showed that the sequestered cells return to the circulation. Vitamin E might facilitate this return by altering the adherence of neutrophils to endothelium. This possibility was tested by measuring the adherence to cultivated rabbit aorta endothelial monolayers of FMLP-stimulated neutrophils from vitamin E-treated rabbits. The percentage of neutrophils adhering was 32.5 +/- 3.5 with vitamin E and 60.0 +/- 7.1, without vitamin E. Thus vitamin E promotes the return of neutrophils to the circulation after chemotactic challenge and may do so by reducing their adherence to endothelium.