Inhibitory effect of neuraminidase on SP-induced histamine release and TNF-alpha mRNA in rat mast cells: evidence of a receptor-independent mechanism

J Neuroimmunol. 1997 May;75(1-2):9-18. doi: 10.1016/s0165-5728(96)00229-9.

Abstract

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.

MeSH terms

  • Animals
  • Female
  • Histamine Antagonists / pharmacology*
  • Histamine Release / drug effects*
  • Mast Cells / drug effects
  • Mast Cells / metabolism*
  • Neuraminidase / pharmacology*
  • Peritoneum / cytology
  • RNA, Messenger / antagonists & inhibitors
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, Cell Surface / physiology
  • Substance P / pharmacology*
  • Tumor Necrosis Factor-alpha / genetics*
  • Uterus / cytology

Substances

  • Histamine Antagonists
  • RNA, Messenger
  • Receptors, Cell Surface
  • Tumor Necrosis Factor-alpha
  • Substance P
  • Neuraminidase