Stress induces substance P in vagal sensory neurons innervating the mouse airways
R. A. Joachim
Departments ofInternal Medicine and Psychosomatics
Search for more papers by this authorL. B. Cifuentes
Pediatric Pneumology and Immunology, Charité Universitätsmedizin, Berlin
Search for more papers by this authorD. Quarcoo
Pediatric Pneumology and Immunology, Charité Universitätsmedizin, Berlin
Search for more papers by this authorA. Fischer
Pediatric Pneumology and Immunology, Charité Universitätsmedizin, Berlin
Search for more papers by this authorR. A. Joachim
Departments ofInternal Medicine and Psychosomatics
Search for more papers by this authorL. B. Cifuentes
Pediatric Pneumology and Immunology, Charité Universitätsmedizin, Berlin
Search for more papers by this authorD. Quarcoo
Pediatric Pneumology and Immunology, Charité Universitätsmedizin, Berlin
Search for more papers by this authorA. Fischer
Pediatric Pneumology and Immunology, Charité Universitätsmedizin, Berlin
Search for more papers by this authorSummary
Background Tachykinins-like substance P (SP) have been shown to play an important role in initiating and perpetuating airway inflammation. Furthermore, they are supposed to be released into tissues in response to stress.
Objective The aim of this study was to investigate the effects of stress alone or in combination with allergic airway inflammation on SP expression in sensory neurons innervating the mouse airways.
Methods Balb/c mice were systemically sensitized to ovalbumin (OVA), followed by allergen aerosol exposure, and compared with non-sensitized controls. Additionally, OVA-sensitized and -challenged and non-sensitized mice were exposed to sound stress. SP expression in airway-specific and overall vagal sensory neurons of the jugular and nodose ganglion complex was analysed using retrograde neuronal tracing in combination with immunohistochemistry. Preprotachykinin A (PPT-A) mRNA, the precursor for SP, was quantified in lung tissue by real-time PCR. Bronchoalveolar lavage (BAL) fluid was obtained, and cell numbers and differentiation were determined.
Results Stress and/or allergic airway inflammation significantly increased SP expression in retrograde-labelled vagal sensory neurons from the mouse lower airways compared with controls [stress: 15.7±0.8% (% of retrograde-labelled neurons, mean±SEM); allergen: 17.9±0.4%; allergen/stress: 13.1±0.7% vs. controls: 6.3±0.3%]. Similarly, SP expression increased in overall vagal sensory neurons identified by the neuronal marker protein gene product (PGP) 9.5 [stress: 9.3±0.6% (% of PGP 9.5-positive neurons, means±SEM); allergen: 12.5±0.4%; allergen/stress: 10.2±0.4% vs. controls: 5.1±0.3%]. Furthermore, stress significantly increased PPT-A mRNA expression in lung tissue from OVA-sensitized and -challenged animals, and immune cells were identified as an additional source of SP in the lung by immunohistochemistry. Associated with enhanced neuronal SP expression, a significantly higher number of leucocytes were found in the BAL following allergen exposure. Further, stress significantly increased allergen-induced airway inflammation identified by increased leucocyte numbers in BAL fluids.
Conclusion The central event of sound stress leads to the stimulation of SP expression in airway-specific neurons. However, in sensitized stressed mice an additional local source of SP (probably inflammatory cells) might enhance allergic airway inflammation.
References
- 1 Lehrer PM, Isenberg S, Hochron SM. Asthma and emotion: a review. J Asthma 1993; 30: 5–21.
- 2 Sandberg S, Paton JY, Ahola S et al. The role of acute and chronic stress in asthma attacks in children. Lancet 2000; 356: 982–7.
- 3 Kilpelainen M, Koskenvuo M, Helenius H, Terho EO. Stressful life events promote the manifestation of asthma and atopic diseases. Clin Exp Allergy 2002; 32: 256–63.
- 4 Liu LY, Coe CL, Swenson CA, Kelly EA, Kita H, Busse WW. School examinations enhance airway inflammation to antigen challenge. Am J Respir Crit Care Med 2002; 165: 1062–7.
- 5 Sandberg S, Jarvenpaa S, Penttinen A, Paton JY, McCann DC. Asthma exacerbations in children immediately following stressful life events: a Cox's hierarchical regression. Thorax 2004; 59: 1046–51.
- 6 Maier SF, Watkins LR. Cytokines for psychologists: implications of bidirectional immune-to-brain communication for understanding behavior, mood, and cognition. Psychol Rev 1998; 105: 83–107.
- 7 Black PH. Stress and the inflammatory response: a review of neurogenic inflammation. Brain Behav Immunol 2002; 16: 622–53.
- 8 Arck PC, Merali FS, Stanisz AM et al. Stress-induced murine abortion associated with substance P-dependent alteration in cytokines in maternal uterine decidua. Biol Reprod 1995; 53: 814–9.
- 9 Joachim RA, Hildebrandt M, Oder J, Klapp BF, Arck PC. Murine stress-triggered abortion is mediated by increase of CD8+TNF-alpha+decidual cells via substance P. Am J Reprod Immunol 2001; 45: 303–9.
- 10 Singh LK, Pang X, Alexacos N, Letourneau R, Theoharides TC. Acute immobilization stress triggers skin mast cell degranulation via corticotropin releasing hormone, neurotensin, and substance P: a link to neurogenic skin disorders. Brain Behav Immunol 1999; 13: 225–39.
- 11 Spanos C, Pang X, Ligris K et al. Stress-induced bladder mast cell activation: implications for interstitial cystitis. J Urol 1997; 157: 669–72.
- 12 Joachim RA, Quarcoo D, Arck PC, Herz U, Renz H, Klapp BF. Stress enhances airway reactivity and airway inflammation in an animal model of allergic bronchial asthma. Psychosomatic Med 2003; 65: 811–5.
- 13 Joachim RA, Sagach V, Quarcoo D, Dinh QT, Arck PC, Klapp BF. Neurokinin-1 receptor mediates stress-exacerbated allergic airway inflammation and airway hyperresponsiveness in mice. Psychosomatic Med 2004; 66: 564–71.
- 14 Kummer W, Fischer A, Kurkowski R, Heym C. The sensory and sympathetic innervation of guinea-pig lung and trachea as studied by retrograde neuronal tracing and double-labelling immunohistochemistry. Neuroscience 1992; 49: 715–37.
- 15 Lundberg JM, Brodin E, Saria A. Effects and distribution of vagal capsaicin-sensitive substance P neurons with special reference to the trachea and lungs. Acta Physiol Scand 1983; 119: 243–52.
- 16 Lundberg JM, Brodin E, Hua X, Saria A. Vascular permeability changes and smooth muscle contraction in relation to capsaicin-sensitive substance P afferents in the guinea-pig. Acta Physiol Scand 1984; 120: 217–27.
- 17 McDonald DM, Mitchell RA, Gabella G, Haskell A. Neurogenic inflammation in the rat trachea. II. Identity and distribution of nerves mediating the increase in vascular permeability. J Neurocytol 1988; 17: 605–28.
- 18 Salonen RO, Webber SE, Widdicombe JG. Effects of neuropeptides and capsaicin on the canine tracheal vasculature in vivo. Br J Pharmacol 1988; 95: 1262–70 issn: 0007–1188.
- 19 Coles SJ, Neill KH, Reid LM. Potent stimulation of glycoprotein secretion in canine trachea by substance P. J Appl Physiol 1984; 57: 1323–7.
- 20 Nieber K, Baumgarten CR, Rathsack R, Furkert J, Oehme P, Kunkel G. Substance P and beta-endorphin-like immunoreactivity in lavage fluids of subjects with and without allergic asthma. J Allergy Clin Immunol 1992; 90: 646–52.
- 21 Fischer A, McGregor GP, Saria A, Philippin B, Kummer W. Induction of tachykinin gene and peptide expression in guinea pig nodose primary afferent neurons by allergic airway inflammation. J Clin Invest 1996; 98: 2284–91.
- 22 Herz U, Braun A, Ruckert R, Renz H. Various immunological phenotypes are associated with increased airway responsiveness. Clin Exp Allergy 1998; 28: 625–34.
- 23 Dinh QT, Groneberg DA, Peiser C et al. Nerve growth factor-induced substance P in capsaicin-insensitive vagal neurons innervating the lower mouse airway. Clin Exp Allergy 2004; 34: 1474–9.
- 24 Knackstedt MK, Zenclussen AC, Hertwig K et al. Th1 cytokines and the prothrombinase fgl2 in stress-triggered and inflammatory abortion. Am J Reprod Immunol 2003; 49: 210–20.
- 25 Forsythe P, Ebeling C, Gordon JR, Befus AD, Vliagoftis H. Opposing effects of short- and long-term stress on airway inflammation. Am J Respir Crit Care Med 2004; 169: 220–6.
- 26 Nogueira PJ, Ferreira HHA, Antunes E, Teixeira NA. Chronic mild prenatal stress exacerbates the allergen-induced airway inflammation in rats. Mediators Inflamm 1999; 8: 119–22.
- 27 Datti F, Datti M, Antunes E, Teixeira NA. Influence of chronic unpredictable stress on the allergic responses in rats. Physiol Behav 2002; 77: 79–83.
- 28 Kiecolt-Glaser J, Dura J, Speicher C, Trask O, Glaser R. Spousal caregivers of dementia victims: longitudinal changes in immunity and health. Psychosom Med 1991; 53: 345–62.
- 29 Esterling BA, Kiecolt Glaser JK, Bodnar JC, Glaser R. Chronic stress, social support, and persistent alterations in the natural killer cell response to cytokines in older adults. Health Psychol 1994; 13: 291–8.
- 30 Dhabhar FS, McEwen BS. Stress-induced enhancement of antigen-specific cell-mediated immunity. J Immunol 1996; 156: 2608–15 issn: 0022–1767.
- 31 Schmid Ott G, Jaeger B, Adamek C et al. Levels of circulating CD8(+) T lymphocytes, natural killer cells, and eosinophils increase upon acute psychosocial stress in patients with atopic dermatitis. J Allergy Clin Immunol 2001; 107: 171–7.
- 32 Redwine L, Snow S, Mills P, Irwin M. Acute psychological stress: effects on chemotaxis and cellular adhesion molecule expression. Psychosom Med 2003; 65: 598–603.
- 33 Viswanathan K, Dhabhar FS. Stress-induced enhancement of leukocyte trafficking into sites of surgery or immune activation. Proc Natl Acad Sci USA 2005; 102: 5808–13.
- 34 Buckley TL, Nijkamp FP. Airways hyperreactivity and cellular accumulation in a delayed-type hypersensitivity reaction in the mouse. Modulation by capsaicin-sensitive nerves. Am J Respir Crit Care Med 1994; 149: 400–7.
- 35 Donnerer J, Schuligoi R, Stein C. Increased content and transport of substance P and calcitonin gene-related peptide in sensory nerves innervating inflamed tissue: evidence for a regulatory function of nerve growth factor in vivo. Neuroscience 1992; 49: 693–8.
- 36 Barnes PJ. Neuropeptides in human airways: function and clinical implications. Am Rev Respir Dis 1987; 136: S77–83.
- 37 Barnes PJ, Chung KF, Page CP. Inflammatory mediators and asthma. Pharmacol Rev 1988; 40: 49–84.
- 38 Kwong K, Wu Z-X, Kashon ML, Krajnak KM, Wise PM, Lee L-Y. Chronic smoking enhances tachykinin synthesis and airway responsiveness in guinea pigs. Am J Respir Cell Mol Biol 2001; 25: 299–305.
- 39 Undem BJ, Hunter DD, Liu M, Haak-Frendscho M, Oakragly A, Fischer A. Allergen-induced sensory neuroplasticity in airways. Int Arch Allergy Immunol 1999; 118: 150–3.
- 40 Lazarov NE. Comparative analysis of the chemical neuroanatomy of the mammalian trigeminal ganglion and mesencephalic trigeminal nucleus. Prog Neurobiol 2002; 66: 19–59.
- 41 Dinh QT, Groneberg DA, Mingomataj E et al. Expression of substance P and vanilloid receptor (VR1) in trigeminal sensory neurons projecting to the mouse nasal mucosa. Neuropeptides 2003; 37: 245–50.
- 42 Dinh QT, Groneberg DA, Peiser C et al. Expression of substance P and nitric oxide synthase in vagal sensory neurons innervating the mouse airways. Regul Pept 2005; 126: 189–94.
- 43 Dinh QT, Mingomataj E, Quarcoo D et al. Allergic airway inflammation induces tachykinin peptides expression in vagal sensory neurons innervating mouse airways. Clin Exp Allergy, 2005; 35: 820–5.
- 44 Peters EM, Handjiski B, Kuhlmei A et al. Neurogenic inflammation in stress-induced termination of murine hair growth is promoted by nerve growth factor. Am J Pathol 2004; 165: 259–71.
- 45 Kollarik M, Dinh QT, Fischer A, Undem BJ. Capsaicin-sensitive and -insensitive vagal bronchopulmonary C-fibres in the mouse. J Physiol (London) 2003; 551: 869–79.
- 46 Aloe L, Bracci Laudiero L, Alleva E, Lambiase A, Micera A, Tirassa P. Emotional stress induced by parachute jumping enhances blood nerve growth factor levels and the distribution of nerve growth factor receptors in lymphocytes. Proc Natl Acad Sci USA 1994; 91: 10440–4.
- 47 Lakshmanan J. Nerve growth factor levels in mouse serum: variations due to stress. Neurochem Res 1987; 12: 393–7.
- 48 Lakshmanan J. Aggressive behavior in adult male mice elevates serum nerve growth factor levels. Am J Physiol 1986; 250: E386–92.
- 49 Spillantini MG, Aloe L, Alleva E, De Simone R, Goedert M, Levi Montalcini R. Nerve growth factor mRNA and protein increase in hypothalamus in a mouse model of aggression. Proc Natl Acad Sci USA 1989; 86: 8555–9.
- 50 Aloe L, Alleva E, De Simone R. Changes of NGF level in mouse hypothalamus following intermale aggressive behaviour: biological and immunohistochemical evidence. Behav Brain Res 1990; 39: 53–61.
- 51 Weinstock JV, Blum A, Walder J, Walder R. Eosinophils from granulomas in murine schistosomiasis mansoni produce substance P. J Immunol 1988; 141: 961–6.
- 52 Bost KL, Breeding SA, Pascual DW. Modulation of the mRNAs encoding substance P and its receptor in rat macrophages by LPS. Reg Immunol 1992; 4: 105–12.
- 53 Killingsworth CR, Shore SA, Alessandrini F, Dey RD, Paulauskis JD. Rat alveolar macrophages express preprotachykinin gene-I mRNA-encoding tachykinins. Am J Physiol 1997; 273: L1073–81.
- 54 Joos GF, Germonpre PR, Pauwels RA. Role of tachykinins in asthma. Allergy 2000; 55: 321–37.
- 55 Springer J, Groneberg DA, Pregla R, Fischer A. Inflammatory cells as source of tachykinin-induced mucus secretion in chronic bronchitis. Regul Pept 2005; 124: 195–201.
- 56 Numao T, Agrawal DK. Neuropeptides modulate human eosinophil chemotaxis. J Immunol 1992; 149: 3309–15.
- 57 Wiedermann FJ, Kahler CM, Reinisch N, Wiedermann CJ. Induction of normal human eosinophil migration in vitro by substance P. Acta Haematol 1993; 89: 213–5.
- 58 Iwamoto I, Nakagawa N, Yamazaki H, Kimura A, Tomioka H, Yoshida S. Mechanism for substance P-induced activation of human neutrophils and eosinophils. Regul Pept 1993; 46: 228–30.
- 59 Schratzberger P, Reinisch N, Prodinger WM et al. Differential chemotactic activities of sensory neuropeptides for human peripheral blood mononuclear cells. J Immunol 1997; 158: 3895–901.
- 60 Ruff MR, Wahl SM, Pert CB. Substance P receptor-mediated chemotaxis of human monocytes. Peptides 1985; 6 (Suppl. 2): 107–11.
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