Sex Steroids and the Induction of Human Neutrophil Cell Death by Monosodium Urate Crystals

Jiann-Jong Chen ； Shinn-Shing Lee ； Chuen-Miin Leu ； Mark Shui-Yu Liu ； Ming-Lin Huang ； Chau-Heng Chien ； Eileen Jea Chien

《Adaptive Medicine》 10卷4期 (2018/12) Pp. 155-160

https://doi.org/10.4247/AM.2018.ABI218

摘要

Gout is characterized by the presence of monosodium urate (MSU) crystals in joints and surrounding tissues. When MSU is detected by tissue, it is treated as ＂danger/ damage＂, and there is rapid recruitment of neutrophils from the circulation into the affected area. Neutrophil death induced by MSU crystals has been found to be strongly related to gout flare-ups. Clinically, males are nearly three times more likely to develop gout than females, but the incidence of gout increases with age for both sex. Sex steroids have immunological properties and are able to modulate various immune factors and are able to relieve excessive inflammation. However, the effect of sex steroids on neutrophil cell death induced by MSU crystals remains unclear. We investigated whether progesterone (P4), estradiol (E2), testosterone (T), and dihydrotestosterone (DHT) individually are able to inhibit neutrophil cell death in the presence of MSU crystals. Neutrophils were isolated from the peripheral venous blood samples of male volunteers. Neutrophil cell death was detected using propidium iodide (PI) assays. The results confirmed that treatment of neutrophils with MSU crystals (600 μg/ml) induced significant cell death within 10 min. Furthermore, when neutrophils were pretreated with various sex steroids (P4, E2, T and DHT) individually for 15 min, the neutrophil cell death induced by MSU crystals was not affected. Sex steroids do not seem to be able to inhibit neutrophil cell lysis induced by MSU crystals and this implies that the rapid responses of neutrophils to sex steroids are not seem involved in gout flare-ups.

關鍵字

monosodium urate ； testosterone ； dihydrotestosterone ； progesterone ； estradiol ； cell lysis ； neutrophil