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Chitin May Be Responsible for Allergies to Shellfish, Dust, and Mold

Researchers at the University of California in San Francisco (UCSF)
have discovered a strong association between chitin and allergy, as
well as asthma. The results of these studies have been published this
week in an early online version of the journal Nature, with a print
version due soon.

Chitin is a polysaccharide properly termed N-acetyl-B-D-glucosamine,
and makes up the rigid exoskeleton of crabs, shrimp, and insects like
dust mites. It is also found in various fungi and molds. While chitin
is the most common biopolymer after cellulose, it is never found in
organisms containing an internal skeleton, such as humans and other
vertebrates. In fact, humans and other animals are genetically
programmed to recognize the substance and eliminate it via an enzyme
called acidic mammalian chitinase (AMCase). Unfortunately, a less
active form of AMCase can also be activated, leading to inflammation
and allergic response to chitin. In severe cases, asthma can result.

For this study, Richard Locksley and his colleagues at UCSF sprayed
aerosolized chitin into the lungs of laboratory mice. The mice
developed an immediate immune response to the chitin, producing the
inflammatory cytokines interleukin (IL) 4 and 13. White blood cells,
termed eosinophils and basophils, then entered the lung tissue and
mounted an attack against the chitin. This kind of acquired immune
response would be expected if the mice had been previously exposed to
chitin, but they had not. Furthermore, the rapid involvement of the
interleukins and white blood cells is characteristic of a classic
allergic response, which relies upon previous exposure to the
allergen.

To find out why the immune systems of mice acted as if they had seen
the chitin before, Locksley and his team tested mice with and without
a special type of white blood cell, called the macrophage. Unlike IL4,
IL13, eosinophils or basophils, the macrophage is part of an
organism's innate, rather than acquired, immune response. Upon
bacterial or viral infection, the macrophage will become activated and
ingest the invading particles, regardless of whether it has dealt with
these particles in the past. Macrophages also produce different
enzymes, such as AMCase, which they use to digest the ingested
particles.

Mice without macrophages did not react against chitin, indicating that
these cells are responsible for initiating the immune response.
Furthermore, mice which produced a greater than average amount of
AMCase showed a lowered acquired immune response to chitin. This
suggests that AMCase, by quickly removing the stimulus from the
system, dampens the body's acquired, and often allergic, response.

Unfortunately, not all people have high levels of AMCase. Also, some
people have AMCase variants, which do little to break down and digest
chitin. These people may be at increased risk for developing allergy
and asthma, especially if exposed repeatedly to high levels of chitin.
For example, there are high rates of asthma among workers at shellfish
processing plants, sometimes as much as 25%. In the population at
large, allergic and asthmatic reactions to shellfish, insects, and
molds are also on the rise. Locksley and his group hope to test
individuals with allergies to chitin, to help determine if they carry
these less active AMCase variants.

One reason for the increasing rates of allergy and asthma among the
general population is the increased microbial sterility of modern
society due to widespread use of antibiotics. By eliminating bacteria
that would feed on chitin, there may be an overabundance of this
substance in the environment, resulting in increased exposure and
immune reaction.
While Locksley states that "asthma is increasing in all industrialized
societies," he hopes that by elucidating the causes and mechanisms of
allergy and asthma, new treatments can be developed soon.

SOURCE:
http://www.associatedcontent.com/article/227891/chitin_may_be_responsible
_for_allergies_pg2.html?cat=58


Butyrate-producing bacteria are natural competitors with molds in human
body surfaces (which includes the GI tract). There appears to be an
evolved, self-regulatory response in Candida that picks up butyrate and
then limits chitin production. Certainly anything that targets
lactobacillus - like antibiotics - or limits its production of butyrate
- a low fiber/high sugar diet - would put one at risk for allergies (in
conjunction, of course, with helminth-naive immune systems).


cerulenin and sodium butyrate inhibit chitin synthesis in Candida
albicans; in vitro studies with isolated membrane-bound chitin synthase
from C. albicans showed neither agent affected the level of either
unactivated or trypsin-activated enzyme activity; more studies utilizing
protoplasts revealed that early in the cell wall regeneration process,
cells treated with cerulenin or butyrate synthesized chitin at a rate
equal to untreated controls as measured by uptake of [3H]GlcNAc but
after 40 min of incubation, the incorporation of [3H]GlcNAc into chitin
is reduced in cells treated with either agent; on the other hand,
samples taken during the same time intervals suggested that the amount
of chitin synthesis in treated and untreated cells was identical; a
marked drop in fluorescence was observed in similar experiments using
polyoxin D, a direct inhibitor of chitin synthase activity; experiments
that measured uptake of [3H]GlcNAc into both whole cells and protoplasts
demonstrated that cerulenin and butyrate had no effect on the transport
of the chitin precursor [PMID 2957042]

Candida albicans germination in liquid medium was inhibited by the
antilipogenic agent cerulenin and sodium butyrate; these inhibitors
prevented germ tube emergence at concentrations of 1 microgram/ml and 20
mM, respectively but neither significantly affected cell viability;
cerulenin treatment resulted in inhibition of lipid biosynthesis but
lipid biosynthetic capabilities remained unaltered in sodium
butyrate-supplemented cultures; because each inhibitor blocks
germination by different mechanisms, their utility in distinguishing
events directly correlated to germination was examined; in this context,
chitin synthase activity was inhibited by both compounds, confirming the
importance of chitin biosynthesis in C. albicans germination [PMID
6357077]

mammalian chitinases digest chitin (N-acetyl-B-D-glucosamine); chitin is
an abundant polysaccharide found in fungi, insects, and parasitic
nematodes (which might be why helminth infection reduce allergies: the
worms need their molecules tolerated by the host¹s immune system);
innate immune host defense against chitin-containing pathogens include
production of chitinases; in human lower airways, acidic mammalian
chitinase (AMCase) is produced in epithelial cells via a Th2-specific,
IL-13-dependent pathway and may act as an inflammatory mediator in
asthma; in eleven controls vs. twenty-two subjects with chronic
rhinosinusitis (CRS), RNA from ethmoid mucosa was collected and patients
were observed over six monthes after sinus surgery to assess for polyp
recurrence; patients were classified as either recalcitrant or
responsive to therapy based on the presence or absence of polyps; AMCase
mRNA was detected in the sinus mucosa of 72% of control subjects and 72%
of patients with eosinophilic CRS with nasal polyps (CRSwNP); expression
of AMCase was significantly greater in recalcitrant CRSwNP than in
treatment-responsive CRSwNP; there was no significant difference in
IL-13 expression between these two groups; AMCase may be an important
mediator in the pathogenesis of Th2 inflammatory diseases of the
respiratory tract; failure of medical and surgical therapy in CRSwNP is
associated with significantly increased expression of AMCase but not Th2
cytokines IL-13 and eotaxin [PMID 16871939]