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

• Published in: Journal of neuroimmunology 1997-05, Vol.75 (1), p.9-18
• Main Authors: Cocchiara, Roberta, Bongiovanni, Antonella, Albeggiani, Giuseppe, Azzolina, Antonina, Lampiasi, Nadia, Di Blasi, Francesco, Geraci, Domenico
• Format: Article
• Language: English
• Subjects: Animals; Competitive PCR; Female; Histamine Antagonists - pharmacology; Histamine Release - drug effects; Mast cell; Mast Cells - drug effects; Mast Cells - metabolism; Neuraminidase; Neuraminidase - pharmacology; Peritoneum - cytology; Rats; Rats, Wistar; Receptors, Cell Surface - physiology; RNA, Messenger - antagonists & inhibitors; RNA, Messenger - metabolism; Substance P; Substance P - pharmacology; TNF- α; Tumor Necrosis Factor-alpha - genetics; Uterus - cytology
• ISSN: 0165-5728; 1872-8421
• 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- α. However, its effect on the heterogeneous response of mast cells (MC) has not been completely studied. We have established that the SP 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- α 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- α 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- α 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- α mRNA levels. The neuraminidase effect was not toxic, since it was not observed in IgE mediated HR and TNF- α mRNA levels. In conclusion, the inhibitory effect of the neuraminidase on the SP-mediated increase of histamine and TNF- α mRNA, suggests that the SP–sialic acid interaction could have a role in the MC heterogeneous response.