Yuh Kuwano

Association of glucocorticoid with stress-induced modulation of body temperature, blood glucose and innate immunity

To know the details of the mechanism on stress-associated responses, attention was first focused on body temperature and blood glucose after stress. Mice were exposed to restraint stress for 6 h. Under this condition, hypothermia (39 degrees C --> 33 degrees C) and hyperglycemia (150 mg/dl --> 350 mg/dl) were induced. Reflecting a stress-associated response, an increase of serum corticosterone (200 ng/ml --> up to 600 ng/ml) was observed. It was examined whether an administration of glucocorticoid induced a similar response. An injection of hydrocortisone (5.0 and 10.0 mg/mouse) simultaneously induced hypothermia and hyperglycemia. The effect on immunoparameters by an injection of hydrocortisone was examined. Although immunosuppression was seen as thymic atrophy and a decrease in the proportion of B cells in the liver, extrathymic T cells and NKT cells were found to be stress-resistant lymphocyte populations, especially in the liver. HSP70 mRNA was indicated to increase in the adrenal glands in response to the hydrocortisone injection. All these responses, including hypothermia, hyperglycemia and immunomodulation, induced by the hydrocortisone injection were suppressed by pre-administration of a glucocorticoid receptor antagonist (RU-486). These results suggest that glucocorticoid is one of the important mediators of the stress-associated responses.

IgA nephropathy-specific expression of the IgA Fc receptors (CD89) on blood phagocytic cells

We analysed the biochemical features of receptors for the Fc‐region of IgA (FcαR, CD89) on blood monocytes and granulocytes of patients with IgA nephropathy (IgAN). FcαR on monocytes of IgAN were found to have a higher Mr (60‐80kD) than those of control monocytes (50–75 kD) and granulocytes (55–75 kD) in both IgAN and controls as shown by immunoprecipitation analysis. Removal of N‐linked carbohydrates from FcαR on monocytes of IgAN revealed a 32–36 kD protein core, the Mr of which was still higher than that of controls (28–32 kD). When FcaL transcripts were analysed by reverse‐transcription‐PCR, only one prominent band was visualized in PCR products from IgAN monocytes. Since the results thus far show that IgAN monocytes express FcαR protein and mRNA differently from granulocytes and control monocytes, PCR products were then cloned and sequenced. The predominant band in PCR products from IgAN monocytes was identical to that of the FcαR a.l transcript, and an additional 10 transcripts containing five novel transcripts were obtained from granulocytes and control monocytes. In three transcripts, we found an insertion sequence between the S2 and EC1 domains, suggesting the existence of a new exon. These results suggest a predominant usage of FcαR a.l among various transcripts of FcαR in IgAN monocytes.

Resistance and augmentation of innate immunity in mice exposed to starvation

Mice were exposed to starvation for 3 days. Body temperature and various parameters were examined. By starvation, body temperature, blood glucose and ACTH decreased, especially on days 2 and 3. The level of corticosterone increased at this time. On the other hand, the number of lymphocytes yielded by the liver, spleen and thymus decreased from day 1 to 3. The change of the distribution of lymphocyte subsets was unique because NK, NKT and extrathymic T cells were stress-resistant in the liver. Conventional T and B cells were stress-sensitive. Reflecting the increased proportion of NK and NKT cells, NK and NKT activities were augmented. The increased proportion of NKT cells produced both IFNgamma and IL-4 (Th0-type profile). The proportion and some functions of granulocytes and macrophages increased on Day 1 after starvation. These results suggest that starvation has a potential to increase the functions of unconventional lymphocytes and myeloid cells.