TOPIC: MCS ad Etiology: Naturally Sensitive
MCS ad Etiology: Naturally Sensitive 8 years 11 months ago #1
MCS people are naturally sensitive - in a descriptive portrait attitude and functional typology - genetically introverted intuitive; counterweight to the rarified air of intuition - an extraordinary dependence on sense impressions - and the development of hypersensitivity of the sense organs (Jung 1921).
MCS can be expected to be a relatively broad set of genetic differences - a natural genetic combination rather than a defect.
Research reported by Veronesi 2001, 2000, Roy 2000 (MCS 15) confirm that mice intolerant of pollution have quantitative differences in receptors and pathways - they are more sensitive.
VERONESI B. AND OORTGIESEN M. NEUROGENIC INFLAMMATION AND PARTICULATE MATTER AIR POLLUTANTS. NEUROTOX 22;795-810 2001:
"...taken together, the above in vivo and in vitro studies suggested that the variable inflammatory sensitivity to PM observed in different mouse strains (ie Balb/C, B6) related to quantitative differences in the neuropeptide, VR1 receptors and acid sensitive pathways found on sensory neurons that innervate the nasal and upper pulmonary airway. Such data showed how genetically determined differences in sensory neural pathways could influence expressions of PM-induced airway inflammation...genetic differences are thought to underlie these variations and have been experimentally demonstrated for ozone (Kleeberger 1995, Zhang 1995), nitrogen dioxide (Holroyd 1997), and diesel exhaust (Ichinose 1997, Miyabara 1998)..."
Because of genetic disposition and environmental exposure - especially a continuous aerosol of combustion byproducts - defects develop in the airway epithelium exposing the nerves.
MEGGS W.J. HYPOTHESIS FOR INDUCTION AND PROPAGATION OF CHEMICAL SENSITIVITY BASED ON BIOPSY STUDIES. ENVIRON HEALTH PERSPECT 1997 (SUPPL 2) 473-78:
....There are defects in the tight junctions between respiratory epithelial cells, focal desquamation of the epithelial cells in places, hypertrophy of glandular structures, lymphocytic infiltrates, and proliferation of sensory nerve fibers...tumor necrosis factor is produced by lymphocytes....
MEGGS W.J. ARCH ENV HEALTH 1999 54(5) 309-11:
....The mechanism by which inflammatory conditions are provoked by chemicals is via chemoreceptors on sensory nerve C-fibers with the release of substance P and other mediators of neurogenic inflammation...progression of inflammation to organ damage is possible to those who continue to be exposed...
Bellina Veronesi and Marga Oortgiesen. National Health Effects and Research Laboratory, Cellular and Molecular Branch, Neurotoxicology Division, US Environmental Protection Agency, Research Triangle Park, North Carolina. Cato Research LTD., Durham, North Carolina.
VERONESI B. & OORTGIESEN M. NEUROGENIC INFLAMMATION AND PARTICULATE MATTER (PM) AIR POLLUTANTS. NEUROTOXICOLOGY 2001 (22):795-810:
.....neurogenic inflammation. In this process, a cascade of cellular and sub-cellular events...the sensory nervous system and its peptidenergic transmitters (i.e. SP, CGRP, NKA) initiate and sustain this inflammation...
...Once released these pro-inflammatory peptides interact with a variety of immune (e.g. lymphocytes, neutrophils, macrophages, eosinophils) and non immune (e.g. smooth muscle, endothelial cells of the vasculature, epithelial cells that line the lumen of the airways and gut, keratinocytes of the skin) target cells...overt symptoms of inflammation (e.g. erythema, edema, vasodilitation, vasoconstriction, mucous secretion) through the phenomenon of the axon reflex... on involvement of the immune system, the initial symptoms of inflammation are exacerbated and perpetuated with resulting tissue damage...
...In normal physiological settings, the respiratory epithelial population and its sensory innervation act reciprocally to influence the growth, differentiation, and homeostasis of each other...These relationships are especially critical to the organism's inflammatory response...In all instances, sensory neurons release 10-200 fold higher levels of IL-6 (pro-inflammatory cytokine) relative to epithelial cells...
...conditions associated with chemical pollutants are characterized by damage to the epithelial barrier that lines the airways...
... Such damage not only results in the loss of critical neuropeptide deactivating enzymes (e.g. NEP) but allows the sensory fiber to physically extend closer to the airway lumen and in closer proximity to the inhaled PM particles...enhanced and prolonged inflammatory events...increased inflammatory response...
Given damage to the airway epithelium, multiplied nerves, and genetic propensity one would expect elevated inflammatory markers in MCS people.
KIMATA, H. EFFECT OF EXPOSURE TO VOLATILE ORGANIC COMPOUNDS ON PLASMA LEVELS OF NEUROPEPTIDES, NERVE GROWTH FACTOR, AND HISTAMINE IN PATIENTS WITH SELF REPORTED MULTIPLE CHEMICAL SENSITIVITY. INT JRNL OF HYG AND ENV H 207;2:159-63 2004.
Elevated levels indicate a wide ranging inflammation - including many other inflammatory substances.
25 normal, MCS, and allergy subjects (total 75) before and after exposure to a painted room.
Substance P (SP), Vasoactive Intestinal Peptide (VIP), Nerve Growth Factor (NGF), and Histamine (H).
For SP Normal 38 before 39 after. MCS 105 before 153 after. Allergy 75 before 74 after.
For VIP Normal 10 before 11 after. MCS 43 before 68 after. Allergy 22 before 21 after.
For NGF Normal 148 before 156 after. MCS 1129 before 1696 after. Allergy 550 before 560 after.
For H Normal 260 before 260 after. MCS 271 before 534 after. Allergy 550 before 560 after.
The normal and allergy group are nearly unchanged after exposure to paint (VOC).
MCS people have elevated markers even before exposure to paint which can be attributed to the defective airway epithelium and ambient combustion aerosol.
What does elevated SP, VIP, and NGF tell us?
OSLUND K. ET AL. ACTIVATION OF NEUROKININ-1 RECEPTORS DURING OZONE INHALATION CONTRIBUTES TO EPITHELIAL INJURY AND REPAIR. AM J RESPIR CELL MOL BIOL 39:279-88 2008:
"...C fibers induce central nervous system - mediated reflexes and also release neuropeptides upon activation, including substance P, neurokinin (NK) A, and calcitonin gene-related peptide (Maggi 1995). Substance P has been shown to be increased in human nasal mucosa and airways after exposure to ozone (Schierhorn 2002, Hazbun 1993)...
...airway epithelial cells expressing NK-1 receptors are distributed down the entire length of the airway...
...substance P acting via NK-1 receptors is an important mediator in orchestrating airway epithelial cell death and proliferation after acute ozone exposure...
...substance P primes and activates human neutrophils for superoxide, H2O2, and nitric oxide production (Sterner-Kock 1999, Tanabe 1996)...
...the pivotal role that the activation of c-fibers, with the subsequent release of substance P, plays in the complex cascade of events that are initiated by the acute inhalation of ozone. This role is not limited to reflex responses, such as rapid shallow breathing, but includes modulation of cellular injury and subsequent proliferation of epithelial cells during repair..."
COSTA S. ET AL. INVOLVEMENT OF SENSORY NERVES AND TRPV1 RECEPTORS IN THE RAT AIRWAY INFLAMMATORY RESPONSE TO TWO ENVIRONMENTAL POLLUTANTS: DIESEL EXHAUST PARTICLES (DEP) AND 1,2-NAPHTHOQUINONE (1,2-NQ). ARCH TOXICOL 84(2):109-117 2010:
"...The environmental chemical 1,2-naphthoguinone (1,2-NQ) is implicated in the exascerbation of airway diseases induced by exposure to diesel exhaust particles (DEP), which involves a neurogenic-mediated mechanism...
...DEP and 1,2-NQ-induced plasma extravasation...mediated by the endogenous release of the pro-inflammatory neuropeptide substance P. This peptide is most usually found in the peripheral sensory c-fibers and its main receptor (NK1) is widely distributed in the cells body...
...in addition to the NK1 receptor (and its endogenous agonist neurokinin A; NKA) plays a role in the inflammatory response evoked by DEP and 1,2-NQ...(Cho 2004, Xia 2004)..."
NILIUS B. ET AL. TRANSIENT RECEPTOR POTENTIAL CATION CHANNELS IN DISEASE. PHYSIOL REV 87:166-217 2007:
"...The major neuropeptides involved in neurogenic inflammation are SP, CGRP, and neuropeptide Y (NPY). Proalgesic, proinflammatory mediators include NGF, protons, histamine, cytokines, chemokines, glutamate, and ATP...
...TRPV1, TRPA1, and TRPM8 are all expressed in sensory neurons in the DRG, TG, and NG. More than 50% of DRG neurons express TRPV1, largely in association with substance P (SP), calcitonin gene-related peptide (CGRP), and the high-affinity nerve growth factor (NGF) receptor TrkA..."
DEERING-RICE ET AL. ELECTROPHILIC COMPONENTS OF DIESEL EXHAUST PARTICLES (DEP) ACTIVATE TRANSIENT RECEPTOR POTENTIAL ANKYRIN-1 (TRPA1): A PROBABLE MECHANISM OF ACUTE PULMONARY TOXICITY FOR DEP. CHEM RES TOXICOL 24;6:950-9 2011:
"...A number of studies have correlated responses to urban PM, including DEP with activation of airway sensory neurons, particularly C and A beta fibers that express Transient Receptor Potential Ankyrin-1 (TRPA1), TRP Vanilloid-1 (TRPV1), and substance P (Hazari 2011, Teles 2009, Anand 2008, Nassenstein 2008, Kobayashi 2005)...
...TRPA1 and V1 are members of the superfamily of ion channels, and numerous TRP receptors including TRPA1, V1-4, and M8 are highly expressed in the respiratory tract where they can function as environmental sensors...
...TRPA1, M8, and V1-4 all respond to specific chemical irritants (Vriens 2009, Venkatachalam 2007, Voets 2005) and activation of either TRPA1 or V1 in pulmonary sensory nerves causes neurogenic inflammation via the release of substance P (SP) and neurokinin A (NKA) (Baraldi 2010)...
...TRPV1, V3, V4, and M8, but seemingly not TRPA1 or V2, are also expressed by airway epithelial cells, and activation of TRPV1 (Teles 2009, Agopyan 2004, 2003, Veronesi 2003, 2001, 2000, Oortgiesen 2000) and TRPM8 (Sabnis 2008) in these cells by prototype agonists and select forms of environmental PM is coupled with proinflammatory cytokine/chemokine production and apoptosis..."
Agopyan N. et al. TRPV1 receptors mediate particulate-matter induced apoptosis. Am J Physiol Lung Cell Mol Physiol 286: L563-572 2004
Agopyan N et al. Negatively charged 2 and 10 micron particles activate vanilloid receptors, increase cAMP, and induce cytokine release. Tox and Appl Pharm 186(2): 63-76 2003
Anand U. et al. TRPA1 receptor localisation in the human peripheral nervous system and functional studies in cultured human and rat sensory neurons. Neurosc Let 438:221-27 2008
Baraldi P. et al. Transient receptor potential ankyrin (TRPA1) Channel as emerging target for novel analgesics and anti-inflammatory agents. J Med Chem 53:5085-5107 2010
Cho A. et al. Determination of 4 quinones in diesel exhaust particles, SRM1649A and atmospheric 2.5. Aer Sc Tech 38:1-14 2004
Costa S. et al. Involvement of sensory nerves and TRPV1 receptors in the rat airway inflammatory response to two environmental pollutants: diesel exhaust particles (DEP) and 1,2-naphthoquinone (1,2-NQ). Arch Toxicol 84(2):109-117 2010
Deering-Rice et al. Electrophilic components of diesel exhaust particles (DEP) activate transient receptor potential ankyrin-1 (TRPA1): a probable mechanism of acute pulmonary toxicity for DEP. Chem Res Toxicol 24;6:950-9 2011
Deluca C. et al. Biological definition of multiple chemical sensiti... from redox state and cytokine profiling and not from polymorphisms of xenobiotic metabolizing enzymes. Tox and Appl Pharm 248: 285-92 2010
Hazari M. et al. TRPA1 and sympathetic activation contribute to increased risk of triggered cardiac arrhythmias in hypertensive rats exposed to diesel exhaust. EHP
Hazbun M. et al. Ozone-induced increases in substance P and 8-epi-prostaglandin F2 alpha in the airways of human subjects. Am j Respir Cell Mol Biol 9:568-72 1993
Holroyd K. et al. Genetic modeling of susceptibility to nitrogen dioxide-induced lung injury in mice. Am J Physiol 273;1-3:L595-602 1997
Ichinose T. et al. Murine strain differences in allergic airway inflammation and immunoglobulin production by a combination of antigen and diesel exhaust particles. Tox 122;3:183-92 1997
Jung C.G. Psychological Types. Princeton University Press and in the Portable Jung Viking Press 1921
Kimata H. Effect of exposure to volatile organic compounds on plasma levels of neuropeptides, nerve growth factor, and histamine in patients with self reported multiple chemical sensitivity. Int J Hyg Env H 207:2 159-63 2004.
Kleeberger S. Genetic susceptibility to ozone exposure. Tox Lett 82-83:295-300 1995
Kobayashi K. et al. Distinct expression of TRPM8,TRPA1, and TRPV1 in rat primary afferent neurons with adelta/c fibers and colocalization with trk receptors. J Comp Neur 493:596-606 2005
Maggi C. et al. Neuropeptides as regulator of airway function: vasoactive intestinal peptide and the tachykinins. Physiol Rev 75:277-322 1995
Meggs W.J. Hypothesis for induction and propagation of chemical sensitivity based on biopsy studies. Env H Perspect 105(2): 473-78 1997
Meggs W.J. et al. Nasal pathology and ultrastructure in patients with chronic airway inflammation (RADS and RUDS) following an irritant exposure. J Tox Clin Tox 34;4: 383 1996
Meggs W.J. and Cleveland Jr. C.H. Rhinolaryngoscopic examination of patients with multiple chemical sensitivity syndrome. Arch Env H 48: 1-14 1993
Miyabara Y. et al. Murine strain differences in airway inflammation caused by diesel exhaust particles. Eur Resp J 11: 291-98 1998
Miyabara Y. et al. Diesel exhaust enhances allergic airway inflamma... and hyperesponsiveness in mice. Am J Resp Crit Care Med 157: 1138-44 1998a
Nassenstein C. et al. Expression and function of the ion channel TRPA1 in vagal afferent nerves innervating mouse lungs. J Phys 586:1595-604 2008
Nilius B. et al. Transient receptor potential cation channels in disease. Physiol Rev 87:166-217 2007
Oortgiesen et al. Residual oil fly ash and charged polymers activate epithelial cells and nociceptive sensory neurons. Am J Physiol Lung Cell Mol Physiol 278: L683-95 2000
Oslund K. et al. Activation of neurokinin-1 receptors during ozone inhalation contributes to epithelial injury and repair. AmJ Respir Cell Mol Biol 39:279-88 2008
Roy et al. Susceptibility to pollutant-induced airway inflammation is neurogenically mediated. EPA EIMS Metadata report 59754 2000
Sabnis A. et al. Human lung epithelial cells express a functional cold-sensing TRPM8 variant. Am J Respir Cell Mol Biol 39: 466-474 2008
Schierhorn K. et al. Ozone-induced release of neuropeptides from human nasal mucosa cells. Int Arch Allerg Immunol 129:145-51 2002
Sterner-Kock A. et al. Substance P primes the formation of hydrogen peroxide and nitric oxide in human neutrophils. J Leukoc Biol 65:1834-40 1999
Tanabe T. et al. Intracellular signalling pathway of substance P-induced superoxide production in human neutrophils. Eur J Pharmacol 299:187-95 1996
Venkatachalam K. & Montell C. TRP Channels: Annual Review of Biochemistry. 76:387-714 2007
Veronesi B. et al. Electrostatic charge activates inflammatory vanilloid (VR1) receptors. Neurotox 24: 463-73 2003
Veronesi B. and Oortgiesen M. Neurogenic inflammation and particulate matter (PM) air pollutants. Neurotox 22: 795-810 2001
Veronesi B. et al. Vanilloid capsaicin receptors influence inflammatory sensitivity in response to particulate matter. Tox Appl Pharm 15;169(1): 66-76 2000
Voets T. et al. Sensing with TRP channels. Nat Chem Biol 1:85-92 2005
Vriens J. et al. Pharmacology of vanilloid transient receptor potential cation channels. 75:1262-79 2009
Xia T. et al. Quinones and aromatic chemical compounds in particulate matter induced mitochondrial dysfunction: implications for ultrafine particle toxicity. EHP 112:1347-58 2004
Zhang L. Differential susceptibility to ozone-induced airways hyperreactivity in inbred strains of mice. Exp Lung Res 21;4:503-18 1995
Tags: Jung, MCS, NK-1, P, SP, TRPA1, TRPV1, chemical, etiology, genetics, More…
The administrator has disabled public write access.
Time to create page: 0.173 seconds