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

Whereas insulin does not stimulate hexose transport in polymorphonuclear leukocytes, we recently reported that C5a causes the leukocytes to take up 2-[(3)H]deoxyglucose. We now find that fMet-Leu-Phe, in a concentration-related manner with an EC(50) (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 EC(50) of 0.6 muM. 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 mug 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.