| Activation of human neutrophils by substance P: effect on FMLP-stimulated oxidative and arachidonic acid metabolism and on antibody-dependent cell-mediated cytotoxicity. | |
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MedLine Citation:
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PMID: 2480329 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We show that the neuropeptide, substance P (SP), a putative mediator of neurogenic inflammation, is a potent regulator of mature, human neutrophil function. SP increased neutrophil cytotoxic activity against an antibody-coated target (P815 cells) in a dose-dependent manner. The maximal effect was noted at an SP concentration of 10(-4) M, when cytotoxicity increased from 4.7 +/- 0.9% to 33.4 +/- 10.3%. This effect was not due to toxicity of SP against the target cells and was antibody-dependent. The level of cytotoxic activity induced by SP was comparable to that described for a number of cytokines, such as GM-CSF, under identical assay conditions. SP-induced cytotoxicity was 73.1 +/- 5.8% of that produced by an optimum concentration of conditioned medium known to contain a number of cytokines which activate mature neutrophils. In addition, SP enhanced FMLP-stimulated superoxide anion production by neutrophils in a dose-dependent fashion. Neutrophils preincubated with medium or 7.5 x 10(-5) M SP and then stimulated with 10(-7) M FMLP produced 7.9 +/- 2.7 and 29.9 +/- 3.7 nmol superoxide anion/10(6) cells, respectively. This priming effect of SP was rapid in onset (less than 15 min) and was maximal from 15 to 60 min, after which it declined. It was not reversed by washing the cells and was temperature dependent. SP did not shift the dose-response curve to FMLP to the left, but it enhanced the response to FMLP in the concentration range 10(-8)-10(-6) M. Similarly SP enhanced LTB4 and 5-HETE production by FMLP-stimulated but not calcium ionophore-stimulated neutrophils. Therefore, these data provide evidence that SP regulates a number of neutrophil functions and suggests a mechanism whereby the nervous system may affect the immune response. Furthermore, the regulatory effects of SP on the neutrophil functions studied appear to be similar to those of a number of cytokines that have been previously implicated in inflammation. |
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Authors:
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A Wozniak; G McLennan; W H Betts; G A Murphy; R Scicchitano |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Immunology Volume: 68 ISSN: 0019-2805 ISO Abbreviation: Immunology Publication Date: 1989 Nov |
Date Detail:
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Created Date: 1990-01-22 Completed Date: 1990-01-22 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 0374672 Medline TA: Immunology Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 359-64 Citation Subset: IM |
Affiliation:
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Department of Thoracic Medicine, Royal Adelaide Hospital, South Australia. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antibody-Dependent Cell Cytotoxicity
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drug effects* Arachidonic Acids / metabolism* Dose-Response Relationship, Drug Humans Hydroxyeicosatetraenoic Acids / biosynthesis Leukotriene B4 / biosynthesis N-Formylmethionine Leucyl-Phenylalanine Neutrophils / drug effects*, immunology, metabolism Substance P / pharmacology* Superoxides / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Arachidonic Acids; 0/Hydroxyeicosatetraenoic Acids; 11062-77-4/Superoxides; 33507-63-0/Substance P; 59880-97-6/N-Formylmethionine Leucyl-Phenylalanine; 71160-24-2/Leukotriene B4 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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