Arachidonate 15-lipoxygenase (arachidonate:oxygen 15-oxidoreductase, EC 1.13.11.33) is a lipidperoxidating enzyme that is implicated in oxidizing low density lipoprotein to its atherogenic form. Monocyte/macrophage 15-lipoxygenase is present in human atherosclerotic lesions. To pursue a basis for induction of the enzyme, which is not present in blood monocytes, the ability of relevant cytokines to regulate its expression was investigated. Interleukin 4 (IL4), among 16 factors tested, specifically induced 15-lipoxygenase mRNA and protein in cultured human monocytes. Interferon y and hydrocortisone inhibited this induction. High-performance liquid chromatography analysis of lipid extracts from IL-4-treated monocytes detected 15-lipoxygenase products esterified to the cellular membrane lipids, indicating enzymatic action on endogenous substrates. Stimulation of IL-4-treated monocytes with calcium ionophore or opsonized zymosan A enhanced the formation of 15-lipoxygenase products. These data identify 1L14 and interferon y as physiological regulators of lipoxygenase expression and suggest an important link between 15-lipoxygenase function and the immune/inflammatory response in atherosclerosis as well as other diseases.

The "loop" diuretics MK-196, bumetanide, piretanide, and furosemide are all potent inhibitors of Cl transport by the dog's tracheal epithelium. In short-circuited tissues, the drugs caused significant decreases in both unidirectional Cl fluxes and in the net flux of Cl toward the lumen; the change in net Cl flux was not significantly different from the change in short-circuit current. The drugs had no effect on active Na absorption. All drugs caused a significant fall in tissue conductance. All drugs, except MK-196, were more potent from the serosal bath; MK-196 was equipotent from either side of the tissue. In experiments with isolated cells, the diuretics caused no significant changes in intracellular Na and K concentrations, a fall in intracellular Cl concentration, and approximately equal falls in Na and Cl influxes. These results suggest that the site of action of these drugs is on a basolateral linked Na-Cl entry process. Additional evidence for such a linked entry process was provided by experiments in which removal of Cl reduced Na influx and removal of Na reduced Cl influx.

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We have developed a preparation of isolated cells from dog tracheal mucosa. The three major cell types of the intact epithelium (ciliated, secretory, and basal) are present in approximately the same proportions as in the intact tissue. These cells show high viability as judged by exclusion of vital dyes, high O2 consumption, and incorporation of amino acids into protein. The intracellular ion contents (in mmol/l cell H2O) are [K]i, 150; [Na]i, 20; and [Cl]i, 50. Ouabain (10(-4) M) causes a rise in [Na]i and a reciprocal loss of intracellular K.