Gulliksson M, Palmberg L, Nilsson G, Ahlstedt S, Kumlin M
Division of Physiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Allergy. 2006 Dec;61(12):1473-9. doi: 10.1111/j.1398-9995.2006.01213.x.
Mannitol-induced bronchoconstriction in subjects with exercise-induced asthma is associated with increased urinary excretion of 9alpha, 11beta-PGF(2), a metabolite of prostaglandin D(2) (PGD(2)) serving as a mast cell marker. It has however been questioned whether or not human mast cells release PGD(2) and leukotriene C(4) (LTC(4)) after osmotic challenge with mannitol in vitro.
Cord blood-derived human mast cells were stimulated osmotically, immunologically or with a combination of both. Supernatants were analysed for PGD(2), LTC(4) and histamine contents with enzyme immunoassays.
Significant release of de novo synthesized eicosanoids, predominantly PGD(2) [12 (8.8, 14) pmol/10(6)cells; median (25th, 75th percentile) but also LTC(4) (0.1 (0.08, 0.15) pmol/10(6) cells] were found in mast cells in vitro in response to 0.7 M mannitol stimulation. A massive release of histamine [70 (5.3)% of total; mean (SEM)] was also found. There were no correlations between the levels of released mediators after mannitol stimulation. In contrast, there was a correlation between release of PGD(2) and LTC(4), following immunological stimulation.
The findings support that hyperosmolar challenge activates mast cells, but different than antigen stimulation.
在运动诱发性哮喘患者中，甘露醇诱发的支气管收缩与9α, 11β-前列腺素F2（PGF2）尿排泄增加有关，PGF2是前列腺素D2（PGD2）的一种代谢产物，可作为肥大细胞标志物。然而，体外甘露醇渗透刺激后人类肥大细胞是否释放PGD2和白三烯C4（LTC4）一直存在疑问。
对脐血来源的人类肥大细胞进行渗透刺激、免疫刺激或两者联合刺激。用酶免疫分析法分析上清液中PGD2、LTC4和组胺含量。
体外实验发现，在0.7M甘露醇刺激下，肥大细胞中大量新合成的类花生酸显著释放，主要是PGD2[12（8.8, 14）pmol/10⁶细胞；中位数（第25、75百分位数）]，还有LTC4（0.1（0.08, 0.15）pmol/10⁶细胞）。还发现组胺大量释放[占总量的70（5.3）%；平均值（标准误）]。甘露醇刺激后释放的介质水平之间无相关性。相反，免疫刺激后PGD2和LTC4的释放之间存在相关性。
这些发现支持高渗刺激可激活肥大细胞，但与抗原刺激不同。
