Distribution and Effects of NO and CO in the Human Upper Respiratory Tract

Jens Andersson

Research output: ThesisDoctoral Thesis (compilation)

Abstract

Mucosal inflammation and airway hyperreactivity are regulated by hundreds of different mediators. The recent discovery of gaseous mediators, produced and active within the airways, opens new possibilities for identification of therapeutic targets and ways to monitor airway inflammation. This thesis is focused on two such mediators, nitric oxide (NO) and carbon monoxide (CO) along with their role in the human upper airways.

NO is a marker and mediator of airway inflammation and has antimicrobial properties. The presented results confirm previous findings of high levels of NO in the paranasal sinuses and support the idea of a special role for the sinuses in airway NO production. They also emphasize the role of the sinuses as reservoirs enabling NO to reach extremely high levels. How NO production in the sinus is regulated is not known, but in a series of pressure chamber experiments it could be demonstrated that a decrease of intrasinusal pressure, such as seen during upper airway allergy or infection (URTI), results in an increase in NO levels within the nasal airways. An enhancement of the nasal airway resistance was seen in parallel, presumably reflecting a vasodilation in the nose. Presented data makes it interesting to speculate in a direct role for the ostium in the regulation of intrasinusal NO production.

A mediator function for CO has been considered in many of the conditions where NO has been proven to be of importance, even though the definite role of CO is still under debate. By the use of immunohistochemistry, enzymes (HO-1, HO-2) responsible for CO production could be demonstrated in middle ear mucosa, along with an enzyme (eNOS) known to induce NO production. This indicates local production of both gases in the middle ear, giving rise to speculations of a role for NO, and perhaps CO as well, in the host defence against invading microorganisms. The findings of CO producing enzymes in the nasal mucosa were prerequisites for a local CO production. Support for an actual production of CO was derived mainly from measurements of CO in the nasal and sinus cavity along with the findings that nose breathing increased the amount of CO found in exhaled air. Increased nasal CO levels could be derived from patients with allergic rhinitis and URTI, indicating a role for CO also as a marker of airway inflammation.

In order to evaluate a possible functional role for CO a series of <i>in vitro</i> experiments were performed with hemin, a HO substrate analog, focusing on neutrophil cell activation and recruitment. Hemin induced a reduction of the surface expression of CD11b and CD66b as examined by flow cytometry, reflecting a down-regulation in neutrophil activity. A similar down-regulation was seen during the pollen season on neutrophils from patients with allergic rhinitis. Furthermore, hemin induced a biphasic effect on neutrophil chemotaxis and random migration. Low levels of hemin increased the migratory response and high levels worked in an inhibitory fashion. Altogether, the CO investigations indicate that CO, endogenously produced within the nasal airways, can function both as a marker of airway inflammation and as a mediator of the inflammatory cellular response.
Original languageEnglish
QualificationDoctor
Awarding Institution
  • Laryngoesophagology, Allergy and Life Quality
Supervisors/Advisors
  • [unknown], [unknown], Supervisor, External person
Award date2002 Jun 15
Publisher
ISBN (Print)91-628-5249-3
Publication statusPublished - 2002

Bibliographical note

Defence details

Date: 2002-06-15
Time: 10:15
Place: Lilla Aulan, MFC (ing 59), UMAS Malmö

External reviewer(s)

Name: Stjärne, Pär
Title: [unknown]
Affiliation: [unknown]

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Subject classification (UKÄ)

  • Otorhinolaryngology

Free keywords

  • mykologi
  • virologi
  • bakteriologi
  • Mikrobiologi
  • mycology
  • transplantation
  • Microbiology
  • bacteriology
  • virology
  • serologi
  • Immunologi
  • serology
  • Otorhinolaryngology
  • audiology
  • auditive system and speech
  • Otorinolaryngologi
  • audiologi
  • hörsel- och talorganen
  • Immunology
  • sinus
  • upper respiratory tract infection
  • nose
  • nitric oxide
  • neutrophil migration
  • middle ear
  • hemin
  • flow cytometry
  • allergy
  • carbon monoxide

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