The neuropeptide substance P stimulates the effector functions of platelets.
Sensory neuropeptides, such as substance P, appear as potent mediators of various immunological reactions, and inhibit or stimulate a wide range of functions of immune inflammatory cells. Platelets were recently shown to participate as effector cells in an IgE or lymphokine-dependent killing of parasites. Substance P and its carboxy-terminal fragment SP (4-11) induce the cytotoxic activity of platelets towards the larvae of Schistosoma mansoni, respectively, by 90% and 40%, whereas the modified C terminal SP, the SP-free acid, exhibits no effect on the platelets. The neuropeptide effects occur at low doses (10(-8) M), are specific as shown by inhibition studies with a substance P antagonist, the D-SP. Binding data obtained after flow cytofluorometry with FITC-SP lead to the conclusion that SP binds specifically to about 20% of the homogenous population of platelets. Moreover, IgE could modulate the SP-dependent functions of platelets since the pre-incubation with myeloma human IgE or with AP2 monoclonal antibodies--known to inhibit the IgE-dependent killing of these cells-leads to a dramatic decrease of the SP dependent cytotoxic activity of platelets towards the larvae. These findings identify a potent mechanism for nervous system regulation of host defence responses.
Centre d'Immunologie, Institut Pasteur Lille, France.
M
M
Damonneville
D
D
Monté
C
C
Auriault
A
A
Capron
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D001792:Blood Platelets / Q000187:drug effects / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D012550:Schistosoma mansoni / Q000276:immunology; D013329:Structure-Activity Relationship; D013373:Substance P / Q000494:pharmacology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D013373:Substance P; D007073:Immunoglobulin E