Quinidine photosensitivity.

Two patients with quinidine photosensitivity had an eczematous dermatitis in a photosensitivity distribution on the face, neck, hands, and forearms. Histologically, both patients showed a bandlike dermal lymphohistiocytic infiltrate with overlying vacuolar changes and necrosis in keratinocytes at the dermoepidermal junction. On phototesting, both patients showed marked sensitivity to UV-A radiation. Sensitivity to UV-B was difficult to assess.

The fluorescence response of chlorotetracycline-loaded human neutrophils. Correlations with lysosomal enzyme release and evidence for a 'trigger pool' of calcium.

Neutrophils labelled with chlorotetracycline (commonly employed as a probe for membrane-bound calcium), underwent rapid decreases in fluorescence upon exposure to N-formylmethionylleucylphenylalanine (more than 1 nM). This decrease was maximal at 1 min and was followed by partial recovery by 3 min. When neutrophils were stimulated with N-formylmethionylleucylphenylalanine and then re-exposed to the same stimulus 3 min later, an additional decrease in chlorotetracycline fluorescence was observed. The magnitude of this second response was inversely related to the concentration of the initial stimulus. Similarly, neutrophils exposed to N-formylmethionylleucylphenylalanine and then restimulated by N-formylmethionylleucylphenylalanine in the presence of cytochalasin B secreted the azurophil granule enzyme beta-glucuronidase; release of the enzyme was also inversely related to the initial concentration of N-formylmethionylleucylphenylalanine. These responses were also time-dependent. Both the second decrement in chlorotetracycline fluorescence and beta-glucuronidase release increased with time allowed between the two administrations of N-formylmethionylleucylphenylalanine. In contrast, decreases in chlorotetracycline fluorescence induced by phorbol myristate acetate showed no comparable recovery phase. When neutrophils, stimulated with phorbol myristate acetate, were then exposed to N-formylmethionylleucylphenylalanine, the second decrement in chlorotetracycline fluorescence diminished as the time allowed between the two stimuli was increased. Secretion of beta-glucuronidase in response to N-formylmethionylleucylphenylalanine was also diminished by increasing the time of exposure to the initial stimulus of phorbol myristate acetate. When N-formylmethionylleucylphenylalanine was used as the initial stimulus, the chlorotetracycline fluorescence response characteristic of phorbol myristate acetate could not be observed for at least 1 min. These results are consistent with the hypothesis that chlorotetracycline serves as a probe of mobilizable membrane-bound 'trigger calcium', a replete pool of which is an obligate requirement for lysosomal enzyme release.

Anion channel blockers inhibit lysosomal enzyme secretion from human neutrophils without affecting generation of superoxide anion.

The role of permeant anions in lysosomal enzyme secretion from human neutrophils was investigated by means of anion-channel-blocking agents: 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS), and pyridoxal phosphate. Lysosomal enzyme release from cytochalasin B-treated human neutrophils stimulated by immune complexes (bovine serum albumin and IgG anti-bovine serum albumin) was inhibited by DIDS, SITS, and pyridoxal phosphate at concentrations that inhibited sulfate fluxes. Enzyme secretion triggered by calcium ionophore A23187 was also inhibited by DIDS and SITS; these agents acted on secretory events subsequent to Ca2+ influx. Neither the species of permeant anion(s) nor the role of anion fluxes in degranulation was identified, although influxes of chloride, hydroxide, or phosphate ions were not critical. In contrast to degranulation, generation of superoxide anions (O2.-) stimulated by immune complex or A23187 was not inhibited by these agents. Ultrastructural cytochemical studies demonstrated that, although lysosomal contents were not discharged from stimulated cells, vacuole formation and lysosome-lysosome fusion were unaffected by SITS or DIDS. Data suggest that anion channel blockers specifically inhibit fusion of lysosomes with the plasma membrane or its invaginations.