Human peripheral neutrophils generated superoxide radicals as assessed by ferricytochrome C reduction in response to activation by the synthetic chemotactic factor, N-formyl-methionyl-leucyl-phenylalanine.

Sodium and potassium ion contents and fluxes of isolated resting human peripheral polymorphonuclear leukocytes were measured . In cells kept at 37°C, [Na]i was 25 mM and [K]i was 120 mM ; both ions were completely exchangeable with extracellular isotopes . One-way Na and K fluxes, measured with 22 Na and 42 K, were all -0 .9 meq/liter cell water -min . Ouabain had no effect on Na influx or K efflux, but inhibited 95 t 7% of Na efflux and 63% of K influx . Cells kept at 0°C gained sodium in exchange for potassium ([Na]i nearly tripled in 3 h) ; upon rewarming, ouabain-sensitive K influx into such cells was strongly enhanced . External K stimulated Na efflux (Km^-1 .5 mM in 140-mM Na medium) . The PNa/PK permeability ratio, estimated from ouabaininsensitive fluxes, was 0.10 . Valinomycin (1 AM) approximately doubled PR .Membrane potential (V.) was estimated using the potentiometric indicator diS-C3(5) ; calibration was based on the assumption of constant-field behavior .External K, but not Cl, affected Vm . Ouabain caused a depolarization whose magnitude depended on [Na]i . Sodium-depleted cells became hyperpolarized when exposed to the neutral exchange carrier monensin ; this hyperpolarization was abolished by ouabain . We conclude that the sodium pump of human peripheral neutrophils is electrogenic, and that the size of the pump-induced hyperpolarization is consistent with the membrane conductance (3 .7-4 .0 /IS/ cm 2) computed from the individual K and Na conductances .

A B S T R A C T The responses of isolated humanperipheral neutrophils to either simultaneous or se-(uential additions of two chemotactic factors were stuidied. Simultaneous additions of formyl-methionylleucyl-phenylalanine (10-100 nM) and the fifth component of complement, C5a (1-10 ,l/ml), evoked partially additive responses of memnbrane depolarization as measured by the fluorescent dye 3,3'-dipropyl-thiocarbocyanine, a transient elevation of intracellular cyclic AMP (cAMP), and superoxide (O2) generation as assessed by ferricytochrome c reduction. Preincubation of the cells with either formyl-methionyl-leucylphenylalanine or C5a alone caused dose-dependent inhibition of the depolarization, the cAMP increase, and O2 release induced by a subsequent exposure to an optimal dose of the same stimuluis, i.e., deactivation occutrred. In contrast, when cells were treated with one chemotactic factor and then exposed to the other stimululs, the cells exhibited a nornial response of peak depolarization, the rise in cAMP, and O2 production i.e., cross-deactivation failed to ocecur. The results imply that deactivation of these phenomena is stimulus specific. Further, these observations are consistent with the hypothesis that cross-deactivation of chemotaxis is mediated by one or more processes that are irrelevant to O2 generation, and that occur distal to the depolarization and cAMP steps in the sequence of neutrophil activation: possibly microtubule polymerization and orientation.

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Eighty‐two patients with sarcoidosis were studied. Arthritis was found in 10 of 64 unselected patients with proved sarcoidosis (15.6 per cent). Clinical analysis of 28 additional patients with the arthritis of sarcoidosis showed two types of arthritis: (1) An acute, transient type which was often associated with the clinical onset of the disease. A chest radiograph usually disclosed enlarged hilar nodes. This type was most common and tended to disappear without residua. (2) A persistent or chronic form which appeared either early or late in the course of the disease, and sometimes led to joint destruction. Radiographs of the affected joints often failed to show abnormalities. Erythema nodosum may or may not be present. Hyperuricemia was found in 20.4 per cent, rheumatoid factor in about 10 per cent, and antinuclear antibodies in 5 per cent of patients with sarcoidosis.