Role of arachidonic acid in stimulation of hexose transport by human polymorphonuclear leukocytes

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Whereas insulin does not stimulate hexose transport in polymorphonuclear leukocytes, we recently reported that C5a causes the leukocytes to take up 2-[3H]deoxyglucose. We now find that fMet-Leu-Phe, in a concentration-related manner with an EC50 (concentration producing 50% of stimulatory activity) of 1.2 nM, causes a 5.5-fold stimulation of deoxyglucose uptake. Moreover, arachidonic acid (5,8,11,14-eicosatetraenoic acid) similarly stimulated deoxyglucose uptake with an EC50 of 0.6 μM. Stimulation by arachidonic acid exhibited structural specificity; five structural analogues of arachidonic acid, including arachidonyl alcohol, 8,11,14-eicosatrienoic acid, 11,14,17-eicosatrienoic acid, 5,8,11,14-eicosatetraynoic acid, and arachidic acid, did not stimulate deoxyglucose uptake. Release and metabolism of arachidonic acid may also be involved in the stimulation of deoxyglucose uptake by fMet-Leu-Phe. Inhibitors of arachidonic acid metabolism (5,8,11,14-eicosatetraynoic acid, nordihydroguaiaretic acid, indomethacin, aspirin, and benzylimidazole) caused parallel changes in the responses to both arachidonic acid and fMet-Leu-Phe. Stimulation of deoxyglucose uptake of polymorphonuclear leukocytes by chemotactic factors or arachidonic acid had the characteristics of carrier-facilitated hexose transport. The response was saturable with increasing concentrations of stimulant or substrate (deoxyglucose). It was stereospecific (inhibited by D-glucose but not by L-glucose) and was inhibited in resting and stimulated cells by 5 μg of cytochalasin B per ml. It was separable from the stimulation of oxidative metabolism; it occurred normally in polymorphonuclear leukocytes from a patient with chronic granulomatous disease (these are incapable of an oxidative metabolic response to membrane stimuli). Thus, stimulation of polymorphonuclear leukocytes is associated with enhanced hexose transport. Moreover, carrier-facilitated hexose transport and arachidonic acid metabolism may be linked, at least in these leukocytes: arachidonic acid mimies the stimulatory effects of chemotactic factors, and blockade of arachidonic acid metabolism inhibits the stimulation of hexose transport by these agents.

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