Kayoko Omura

Macrophage‐colony stimulating factor (M‐CSF) enhances proteinuria and recruitment of macrophages into the glomerulus in experimental murine nephritis

In this study, we examined the effects of macrophage‐colony stimulating factor (M‐CSF) on glomerular macrophages in lipopolysaccharide (LPS)‐induced murine nephritis. Mice injected intraperitoneally with either M‐CSF plus LPS, LPS alone, M‐CSF alone or saline every day for 8 days were examined for the degree of urine albumin excretion and lymphocyte‐function associated antigen‐1‐positive (LFA‐1+) cells in peripheral blood as well as renal pathology. From our results, LPS or M‐CSF combined with LPS emphasized the degree of proteinuria, glomerular deposition of immunoglobulins and mesangial proliferation, associated with accumulation of macrophages in the glomeruli. However, in immunohistological examination of kidneys from these nephritic mice, neither intercellular adhesion molecule‐1 (ICAM‐1), which may play an important role in the recruitment of macrophages into glomeruli, M‐CSF receptor nor the number of LFA‐1+ cells in peripheral blood was enhanced by M‐CSF. On the other hand, M‐CSF alone induced neither proteinuria nor any pathological changes and did not increase the number of glomerular Mac‐1+ cells above that in saline‐treated controls. These results indicate that M‐CSF does not directly cause glomerulonephritis but might participate in accelerating the glomerular inflammatory process by stimulating a potent chemoattractant to recruit monocytes‐macrophages into the glomeruli.

Development of nephrotic syndrome in a patient with acute myeloblastic leukemia after treatment with macrophage—Colony-stimulating factor

We describe a patient with acute myeloblastic leukemia (AML) who developed nephrotic syndrome after receiving several courses of chemotherapy, including macrophage-colony-stimulating factor (M-CSF). At the onset of nephrotic syndrome, the patient remained in a hematological remission. A renal biopsy showed diffuse mesangial proliferation with marked glomerular infiltration of macrophages and massive subendothelial and mesangial deposits. After the institution of the combined therapy with corticosteroid, anticoagulant, and dipyridamole, urinary protein excretion was attenuated to less than 1.0 g/day. It should be emphasized that the recurrence of nephrotic syndrome was observed after the following chemotherapy, including M-CSF, whereas the bone marrow still remained completely remitted. In contrast, after the last course of chemotherapy, which did not include M-CSF, urinary protein excretion was not enhanced. Of note is that the renal histology at autopsy showed a remarkable improvement of mesangial hypercellularity with concomitant reduction in the number of glomerular macrophages. These evolutional changes in both proteinuria and glomerular histology suggest a close linkage between the M-CSF treatment and macrophage-related glomerular injury. The possibility can be raised that M-CSF accelerated the underlying renal disease in this case through enhancing macrophage accumulation into the glomerulus, leading to the development of nephrotic syndrome.

Effects of enprostil on gastric endocrine secretion during chronic administration of lansoprazole

We investigated changes in the secretory kinetics of gastric endocrine cells related to the administration of lansoprazole, and the effects of enprostil on these altered kinetics. Male Wistar-derived 8-week-old rats were allotted to a control group, a lansoprazole administration group, an enprostil administration group, and a lansoprazole + enprostil administration group. Lansoprazole (30 mg/kg once a day for 4 weeks) and enprostil (10μg/kg twice a day for 4 weeks) were administered into the gastric lumen with a gastric tube. At this time, blood was collected and immunohistological staining of gastric endocrine cells was conducted to investigate the secretory kinetics. Lansoprazole administration induced hypergastrinemia, increase of gastrin cells, and increase of enterochromaffin-like cells. Enprostil administration induced increase of somatostatin cells. The group administered lansoprazole + enprostil exhibited significant decreases in serum gastrin level, total gastrin cell count, and total enterochromaffin-like cell count, compared with the group administered lansoprazole alone. These findings suggest that enprostil may ameliorate the alteration in gastric endocrine secretion produced by the chronic administration of lansoprazole.

EFFECT OF PIRENZEPINE ON GASTRIC ENDOCRINE CELL KINETICS DURING LANSOPRAZOLE ADMINISTRATION

Abstract: We studied the effect of pirenzepine on gastric secretion kinetics in rats in a hypochlorhydric state induced by lansoprazole, a proton pump inhib-itor. Pirenzepine was administered intramuscularly at a dosage of 20 mg/kg twice daily; and lansorprazole, subcutaneously at 50 mg/kg once daily, both every day for 4 weeks. After the 4-week treatment, serum gastrin and plasma somatostatin levels were determined by radioimmunoassay. In addition, gastrin cells, somatostatin cells, and enterochromaffin-like cells were immunostained and counted. Serum gastrin levels were elevated, and gastrin and enterochromaffin-like cell numbers increased in the group on lansoprazole alone, compared with these values in the control group (which received distilled water). In the group on the lansoprazole and pirenzepine combination, serum gastrin levels decreased, and gastrin and enterochromaffin-like cell numbers were significantly decreased, compared with the respective variables in the group on lansoprazole alone, while the number of somatostatin cells increased in the group on the combination. Plasma somatostatin levels did not vary significantly in any group. It was thus demonstrated that pirenzepine corrects the abnormal gastric secretion kinetics resulting from treatment with lansoprazole alone, such as hypergastrinemia and gastrin and enterochromaffin-like cell hyperplasia.