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Peptidergic modulation of phagocyte activity
68
Pharmac ological Research. Vol. 22. Supplemenl 2. 1990
PEPTIDERGIC MODULATION OF PHAGOCYTE ACTIVITY S. BL'Uoelleschi It , A. Muzzolini & R. Fantozzi * Dept. Pharmacology, Univ. Florence, V.le G.B. Morgagni, 65, 50134 Firenze (Italy); lnst. Pharmacology, Univ. Ferrara, Via Fossato di Mortara, 64B, 44100 Ferrara (Italy). The involvement of Substance P (SP) in the so-called "neurogenic iE. flammation" prompted us to evaluate the effects of this neuropeptide on the activity of phagocytes, such as neutrophils and alveolar macrophages (AM). AM were isolated from the broncho-alveolar lavage of actively senzitized and not sensitized guinea-pigs and purified by adhesion. Superoxide anion (0;) production, which was chosen as a p~ rameter of cell functioning, was measured by the superoxide-dismutase inhibitable cytochrome C reduction. Mammalian tachykinins evoked 0; production from guinea-pig AM, with the following order of potency: neurokinin A (ED = 0.1 nM) SP (ED = 0.7 nM) > neurokinin B 50 50 (ED = 1.3 nM). In experiments performed on actively sensitized gUi 5o nea-pigs, dose-response curves for SP and neurokinin A were shifted to the left. Similar dose-response curves were obtained by assaying PGE production. Neutrophils were isolated from ~e peripheral blood 2 of human healthy donors. Stimulating effects on O· ·production (which 2 ~ was chosen as a parameter of neutrophil functioning) by SP were very weak (in comparison with known stimuli, such as the chemotactic peptide FMLP and PAF) and recorded at 10 - 100 uM only. However, when neutrophils were pretreated with different concentrations of SP (lnM - 10 uM) and then challenged with FMLP or PAF, an enhanced 0; produ~ tion was observed. Neutrophil response to FMLP was enhanced also when the cells were challenged by a combination of FMLP and PF4 (Pl~ telet Factor 4), a protein which is released by activated platelets. While the interaction between FMLP and PF4 indicates a molecular mechanism of neutrophil-platelet interactions, the ability of SP to mo dulate phagocyte activity further supports the idea that the nervous system modulates immune responses.
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1043---{j618/90/22II0068~1/$03.00/0
© 1990 The Italian Pharmacological Society
Pharmac ological Research. Vol. 22. Supplemenl 2. 1990
PEPTIDERGIC MODULATION OF PHAGOCYTE ACTIVITY S. BL'Uoelleschi It , A. Muzzolini & R. Fantozzi * Dept. Pharmacology, Univ. Florence, V.le G.B. Morgagni, 65, 50134 Firenze (Italy); lnst. Pharmacology, Univ. Ferrara, Via Fossato di Mortara, 64B, 44100 Ferrara (Italy). The involvement of Substance P (SP) in the so-called "neurogenic iE. flammation" prompted us to evaluate the effects of this neuropeptide on the activity of phagocytes, such as neutrophils and alveolar macrophages (AM). AM were isolated from the broncho-alveolar lavage of actively senzitized and not sensitized guinea-pigs and purified by adhesion. Superoxide anion (0;) production, which was chosen as a p~ rameter of cell functioning, was measured by the superoxide-dismutase inhibitable cytochrome C reduction. Mammalian tachykinins evoked 0; production from guinea-pig AM, with the following order of potency: neurokinin A (ED = 0.1 nM) SP (ED = 0.7 nM) > neurokinin B 50 50 (ED = 1.3 nM). In experiments performed on actively sensitized gUi 5o nea-pigs, dose-response curves for SP and neurokinin A were shifted to the left. Similar dose-response curves were obtained by assaying PGE production. Neutrophils were isolated from ~e peripheral blood 2 of human healthy donors. Stimulating effects on O· ·production (which 2 ~ was chosen as a parameter of neutrophil functioning) by SP were very weak (in comparison with known stimuli, such as the chemotactic peptide FMLP and PAF) and recorded at 10 - 100 uM only. However, when neutrophils were pretreated with different concentrations of SP (lnM - 10 uM) and then challenged with FMLP or PAF, an enhanced 0; produ~ tion was observed. Neutrophil response to FMLP was enhanced also when the cells were challenged by a combination of FMLP and PF4 (Pl~ telet Factor 4), a protein which is released by activated platelets. While the interaction between FMLP and PF4 indicates a molecular mechanism of neutrophil-platelet interactions, the ability of SP to mo dulate phagocyte activity further supports the idea that the nervous system modulates immune responses.
>
1043---{j618/90/22II0068~1/$03.00/0
© 1990 The Italian Pharmacological Society