Vol. 94 No.5 May 2001
Pathogenesis of Nasal Mucus Hypersecretion in Chronic Sinusitis
Yuichi Majima (Mie University)
Nasal mucus hypersecretion is a feature of
chronic sinusitis (CS). Bacterial infection,which initiates neutrophil
accumulation in the nose and sinuses is an initial cause of CS. The specific
neutrophil products to stimulate mucus glycoprotein (MGP) secretion are
neutrophil elastase, cathepsin G and platelet-activating factor. Eicoanoids are
a group of lipids derived from arachidonic acid that is released from the cell
membranes of inflammatory and epithelial cells, and also contribute to MGP
production. Bacterial products, such as lipopolysaccharide and elastase from
some bacteria, are potent secretagogues. Such products derived from inflammatory
cells and bacterias are retained in sinuses for a long time because of
obstruction of the sinus ostium and mucociliary dysfunction of the nose and
sinuses. Submucosal gland cells are hyperplastic and hypertrophic but goblet
cells are not, and the major source of MGP hypersecretion is submucosal gland
cells rather than goblet cells. The role of neural innervation of submucosal
glands on MGP overproduction has not yet to be elucidated.
The rheologic properties of nasal mucus
from CS patients are much higher than the optimal viscoelasticity for
mucociliary transport. Since MGP mainly determines the high viscosity and the
high elasticity of nasal mucus, a control of MGP production could contribute to
the normalization of abnormal viscoelasticity, and result in the improvement of
mucociliary clearance. This is accomplished by removing the sinus retention that
contains many secretagogues. Although current pharmacological approaches to
airway mucus production are limited, glucocorticoid appears to be the most
effective among the few useful drugs. The effect of 14-membered macrolide
antibiotics on MGP production is still controversial. Some mucolytic agents
change the conformations of MGP and lead to the reduction of viscoelasticity,
when they are administered topically or systemically.
The
mechanisms of nasal mucus hypersecretion are also discussed in relation to the
etiology of CS.