Keita Hosoi

Cell shrinkage evoked by Ca2+‐free solution in rat alveolar type II cells: Ca2+ regulation of Na+–H+ exchange

The effects of intracellular Ca2+ concentration, [Ca2+]i, on the volume of rat alveolar type II cells (AT‐II cells) were examined. Perfusion with a Ca2+‐free solution induced shrinkage of the AT‐II cell volume in the absence or presence of amiloride (1 μm, an inhibitor of Na+ channels); however, it did not in the presence of 5‐(N‐methyl‐N‐isobutyl)‐amiloride (MIA, an inhibitor of Na+–H+ exchange). MIA decreased the volume of AT‐II cells. Inhibitors of Cl−–HCO3− exchange, 4,4′‐diisothiocyanostilbene‐2,2′‐disulfonic acid (DIDS) and 4‐acetamido‐4′‐isothiocyanatostilbene‐2,2′‐disulfonic acid (SITS) also decreased the volume of AT‐II cells. This indicates that the cell shrinkage induced by a Ca2+‐free solution is caused by a decrease in NaCl influx via Na+–H+ exchange and Cl−–HCO3− exchange. Addition of ionomycin (1 μm), in contrast, induced cell swelling when AT‐II cells were pretreated with quinine and amiloride. This swelling of the AT‐II cells is not detected in the presence of MIA. Intracellular pH (pHi) measurements demonstrated that the Ca2+‐free solution or MIA decreases pHi, and that ionomycin increases it. Ionomycin stimulated the pHi recovery after an acid loading (NH4+ pulse method), which was not noted in MIA‐treated AT‐II cells. Ionomycin increased [Ca2+]i in fura‐2‐loaded AT‐II cells. In conclusion, the Na+–H+ exchange activities of AT‐II cells, which maintain the volume and pHi, are regulated by [Ca2+]i.

Delayed shrinkage triggered by the Na+–K+ pump in terbutaline‐stimulated rat alveolar type II cells

Terbutaline (10 μm) induced a triphasic volume change in alveolar type II (AT‐II) cells: an initial shrinkage (initial phase) followed by cell swelling (second phase) and a gradual shrinkage (third phase). The present study demonstrated that the initial and the third phases are evoked by the activation of K+ and Cl− channels and the second phase is evoked by the activation of Na+ and Cl− channels. Ouabain blocked the third phase, although it did not block the initial and second phases. This suggests that the third phase is triggered by the Na+–K+ pump. Tetraethylammonium (TEA, a K+ channel blocker) decreased the volume of AT‐II cells and enhanced the terbutaline‐stimulated third phase, although quinidine, another K+ channel blocker, increased the volume of AT‐II cells. The TEA‐induced cell shrinkage was inhibited by ouabain, suggesting that TEA increases Na+–K+ pump activity. Ba2+, 2,3‐diaminopyridine and a high [K+]o (30 mm) similarly decreased the volume of AT‐II cells. These findings suggest that depolarization induced by TEA increases Na+–K+ pump activity, which increases [K+]i. This [K+]i increase, in turn, hyperpolarizes membrane potential. Valinomycin (a K+ ionophore), which induces hyperpolarization, decreased the volume of AT‐II cells and enhanced the third phase in these cells. In conclusion, in terbutaline‐stimulated AT‐II cells, an increase in Na+–K+ pump activity hyperpolarizes the membrane potential and triggers the third phase by switching net ion transport from NaCl entry to KCl release.

Multiple Cytokines-Producing Pleomorphic Carcinoma of Lung with Metastasis to the Small Intestine

A 58-year-old man underwent upper lobectomy for primary pleomorphic carcinoma of the lung. Nine months later, the pleomorphic carcinoma was recurred with marked peripheral leukocytosis and an elevated C-reactive protein. Chest and abdominal computed tomography (CT) revealed enlarged mediastinal lymph nodes and a bulky tumor in the small intestine. An enterectomy was performed and the intestinal tumor was removed. Immunostaining revealed tumor cells positive for G-CSF and TNF-α as well as an increased level of serum G-CSF and TNF-α. We describe a rare case of G-CSF and TNF-α producing pleomorphic carcinoma of the lung with metastasis to the small intestine.

Pleural vasculitides of microscopic polyangiitis with asbestos-related plaques

A 69‐year‐old man who had been exposed to asbestos for approximately 40 years presented with the complaint of fever and pleuritic chest pain on the right side on deep inspiration. Chest X‐ray films showed pleural effusion in the right side. Initial antibiotic treatment was ineffective. The hyaluronic acid level was high in the pleural effusion but no malignant mesotheliomal cells were seen with blind pleural biopsy. Blood chemistry showed a remarkable high titer of myeloperoxidase anti‐neutrophil cytoplasmic antibody (MPO‐ANCA) and open renal biopsy suggested crescentic glomerulonephritis. The precise pathological examination on the pleura obtained by the open pleural biopsy showed vasculitides and plaque leading to diagnosis of microscopic polyangiitis (MPA). This is a rare case of MPA seen in the pleural arteries.