Ho WZ, Lai JP, Zhu XH, Uvaydova M, Douglas SD. Human monocytes and macrophages express substance P and neurokinin-1 receptor
Division of Immunologic and Infectious Diseases, Joseph Stokes Jr. Research Institute at the Children's Hospital of Philadelphia, PA 19104, USA. The Journal of Immunology
(Impact Factor: 4.92).
We present data demonstrating the gene expression of substance P and its receptor in human peripheral blood-isolated monocytes and macrophages. Using the RT-PCR assay, preprotachykinin-A (substance P) mRNA is detected in human peripheral blood-isolated monocytes and macrophages. Among the alpha, beta, and gamma transcripts of the substance P gene, only the beta and gamma transcripts are detectable in these cells. By Southern blot assay these RT-PCR-amplified transcripts are recognized using a specific substance P probe. Sequence analysis of the RT-PCR products from both monocytes and macrophages also confirmed the structure of these transcripts, which are identical to those found in human neuronal cells. At the protein level, both human monocytes and macrophages produced endogenous substance P as determined by an enzyme immunoassay. Capsaicin, a vanillyl fatty acid amide (ingredient of hot pepper), released substance P from both human monocytes and macrophages. In addition, using nested RT-PCR analysis, we identified the presence of mRNA for neurokinin-1 receptor (the receptor for substance P) in human peripheral blood-isolated monocytes and macrophages, which was confirmed by DNA sequencing analysis. The demonstration that human monocytes and macrophages express substance P and its receptor support the notion that substance P is biologically involved in regulating the functions of these cells in an autocrine fashion.
Available from: Jingjing Wang
- "Previous studies have suggested that tachykinins, including substance P and neurokinin A as the important neuropeptides, can potentiate cholinergic neurotransmission in the CNS and postganglionic nerve terminals , . This neuropeptides was also synthesized in non-neuronal cells, such as macrophages and released in inflammatory diseases . Because their receptors NK1 (for SP) and NK2 (for NKA) were located in the epithelial cells, vessels, submucosal glands and smooth muscle of respiratory system, tachykinins most likely showed a more important constricting effect on the smaller bronchi and microvascular of the bronchi and alveoli in asthmatic subjects , , , . "
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ABSTRACT: Enterovirus 71 (EV71) is the major pathogen responsible for fatal hand, foot and mouth disease (HFMD). Our previous work reported on an EV71-infected rhesus monkey infant model that presented with histo-pathologic changes of the central nervous system (CNS) and lungs. This study is focused on the correlated modulation of gene expression in the peripheral blood mononuclear cells (PBMCs) from EV71-infected rhesus monkey infants. The expression of more than 500 functional genes associated with multiple pathways was modulated. The expression of genes associated with immune inflammatory responses was up-regulated during the period from days 4 to 10 post-infection. The expression of two genes (TAC1 and IL17A), which play major roles in inflammatory reactions, was remarkably up-regulated during the infection period. Furthermore, a higher expression level of the TAC1 gene was identified in the CNS compared to the lungs, but a high expression level of the IL-17A gene was observed in the lungs and not in the CNS. The results of this study suggest at least two facts about EV71 infection, which are that: the TAC1 gene that encodes substance P and neurokinin-A is present in both PBMCs and the hypothalamus; and the up-regulation of IL-17A is sustained in the peripheral blood.
Available from: George Anderson
- "SP has been also demonstrated in human non-neuronal cell types, including endothelial cell, eosinophils, lymphocytes, and in Leydig cells (Aliakbari et al., 1987; Chiwakata et al., 1991; Lai et al., 1998; Linnik and Moskowitz, 1989; Milner et al., 1990). Monocytes and macrophages also express both SP and the neurokinin-1 (NK-1) receptor (Ho et al., 1997). SP could not only act as a neurotransmitter but also as a functional regulator in an autocrine and/or paracrine manner. "
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ABSTRACT: Substance P (SP) after binding to the neurokinin-1 (NK-1) receptor regulates many biological functions. Both SP and the NK-1 receptor are expressed in human normal placenta cells, monocytes, and macrophages. However, to our knowledge, the presence of both SP and the NK-1 receptor in macrophages of the placenta, the Hofbauer cells, is unknown. We demonstrate by immunohistochemistry in human normal placenta samples the presence of both SP and NK-1 receptors in the cytoplasm and in the nucleus of Hofbauer cells. The findings suggest a functional role of the SP/NK-1 receptor system in the physiology and pathophysiology of Hofbauer cells in the human placenta. Microsc. Res. Tech., 2013. © 2013 Wiley Periodicals, Inc.
Available from: Ke-fang Lai
- "Neuropeptides have been described having a neuronal origin, but there is increasing evidence that these peptides may be synthesized and released from immune cells such as macrophages, lymphocytes and monocytes –.Inflammatory cytokines may increase the expression of neuropeptide genes in inflammatory cells, so that inflammatory cell become a major source of the neuropeptide at the inflammatory site . "
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Asthma is a complex pulmonary inflammatory disease characterized by the hyper-responsiveness, remodeling and inflammation of airways. Formaldehyde is a common indoor air pollutant that can cause asthma in people experiencing long-term exposure. The irritant effect and adjuvant effect are the two possible pathways of formaldehyde promoted asthma.
To explore the neural mechanisms and adjuvant effect of formaldehyde, 48 Balb/c mice in six experimental groups were exposed to (a) vehicle control; (b) ovalbumin; (c) formaldehyde (3.0 mg/m3); (d) ovalbumin+formaldehyde (3.0 mg/m3); (e) ovalbumin+formaldehyde (3.0 mg/m3)+HC-030031 (transient receptor potential ankyrin 1 antagonist); (f) ovalbumin+formaldehyde (3.0 mg/m3)+ capsazepine (transient receptor potential vanilloid 1 antagonist). Experiments were conducted after 4 weeks of combined exposure and 1-week challenge with aerosolized ovalbumin. Airway hyper-responsiveness, pulmonary tissue damage, eosinophil infiltration, and increased levels of interleukin-4, interleukin-6, interleukin-1β, immunoglobulin E, substance P and calcitonin gene-related peptide in lung tissues were found in the ovalbumin+formaldehyde (3.0 mg/m3) group compared with the values seen in ovalbumin -only immunized mice. Except for interleukin-1β levels, other changes in the levels of biomarker could be inhibited by HC-030031 and capsazepine.
Formaldehyde might be a key risk factor for the rise in asthma cases. Transient receptor potential ion channels and neuropeptides have important roles in formaldehyde promoted-asthma.
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