Influence of substance P and substance P--sequences on immunocompetent cells

The influence of substance P (SP) and substance P-sequences on spleen cell cultures of mice and on rat lymph node mononuclear cells was studied. SP and the N-terminal fragments SP(1-4) and SP(1-7) were capable of inducing the secretion of lymphokines with chemotactic properties for polymorphonuclear leukocytes and lymphocytes. The peak of the dose-response curves appeared in a concentration range of 10(-11) to 10(-10) mol/l. The predominant migratory stimulatory activity was found at a molecular mass of 12,000 and 23,000 dalton and an inhibitory activity at 35,000 dalton. The C-terminal part of the peptide, SP(6-11), SP(7-11), SP(8-11), SP(9-11), was not able to induce such lymphokine secretion. The experimental results display the importance of the N-terminal fragment for the lymphokine secretion, and support the hypothesis that SP is also a peptide with modulatory functions in the immune response.