Cocchiara R, Bongiovanni A, Albeggiani G, Azzolina A, Lampiasi N, Di Blasi F, Geraci D
Istituto di Biologia dello Sviluppo, CNR, Palermo, Italy.
J Neuroimmunol. 1997 May;75(1-2):9-18. doi: 10.1016/s0165-5728(96)00229-9.
The neuropeptide substance P (SP) is a mediator of neuro-inflammation and can play a role by induction of histamine release (HR) and TNF-alpha. However, its effect on the heterogeneous response of mast cells (MC) has not been completely studied. We have established that the SR can induce 25% of HR in highly purified rat uterine MC at diestrous but not at proestrous phases of the reproductive cycle and 88% of HR in peritoneal mast cells (PMC). We also found 2.2 fold increase in TNF-alpha mRNA at diestrous, in SP stimulated uterine MC versus control and 2.7 fold increase in PMC; RT and competitive PCR were used to amplify the TNF-alpha mRNA. We have thereafter investigated the mechanism whereby the binding of SP to sialic acid on the MC membrane, could trigger secretion of histamine and induction of TNF-alpha mRNA. The neuraminidase pretreatment (0.1 U/ml) inhibited SP-stimulated HR from either uterine MC and PMC (98% and 50%, respectively) and totally inhibited SP-stimulated TNF-alpha mRNA levels. The neuraminidase effect was not toxic, since it was not observed in IgE mediated HR and TNF-alpha mRNA levels. In conclusion, the inhibitory effect of the neuraminidase on the SP-mediated increase of histamine and TNF-alpha mRNA, suggests that the SP-sialic acid interaction could have a role in the MC heterogeneous response.
神经肽P物质（SP）是神经炎症的介质，可通过诱导组胺释放（HR）和肿瘤坏死因子-α（TNF-α）发挥作用。然而，其对肥大细胞（MC）异质性反应的影响尚未得到充分研究。我们已经确定，在生殖周期的动情间期，SP可诱导高度纯化的大鼠子宫MC释放25%的HR，但在动情前期则不能；而在腹膜肥大细胞（PMC）中，SP可诱导88%的HR释放。我们还发现，在动情间期，SP刺激的子宫MC中TNF-α mRNA水平相较于对照组增加了2.2倍，在PMC中增加了2.7倍；采用逆转录和竞争性PCR扩增TNF-α mRNA。此后，我们研究了SP与MC膜上唾液酸结合从而触发组胺分泌和诱导TNF-α mRNA的机制。神经氨酸酶预处理（0.1 U/ml）可抑制子宫MC和PMC中SP刺激的HR释放（分别为98%和50%），并完全抑制SP刺激的TNF-α mRNA水平。神经氨酸酶的作用无毒，因为在IgE介导的HR和TNF-α mRNA水平中未观察到这种作用。总之，神经氨酸酶对SP介导的组胺和TNF-α mRNA增加的抑制作用表明，SP-唾液酸相互作用可能在MC的异质性反应中发挥作用。
