Ironjustic
Mon, Mar-10-08, 17:16
Allergic Response Tied to Lipid Molecules in Cell Membrane
7 March 2008--A team of Penn State University researchers is
the first to demonstrate that lipid molecules in cell
membranes participate in mammals' reactions to allergens in a
living cell. The finding will help scientists better
understand how allergy symptoms are triggered, and could
contribute to the creation of improved drugs to treat them.
The work will be reported in the 14 March issue of the Journal
of Biological Chemistry.
The team studied clusters of cholesterol-rich lipid molecules
that they believe serve as platforms for the receptors that
receive antibodies, the proteins that protect the body from
allergens. In this case, the team examined IgE antibodies,
which upon binding to their receptors initiate a cell's
release of histamine--the substance that causes the
unpleasant, but beneficial, mucous production, congestion, and
itchiness associated with allergies. "This research is
basically the molecular foundation for why many people sneeze
in the spring," said Ahmed Heikal, an associate professor in
the Department of Bioengineering and a leader of the project.
While the idea that lipid clusters--also known as lipid
domains--are involved in the allergic response is not new, the
Penn State team is the first to document this connection in a
living cell under physiological conditions. "No one has
observed the domains in action because they are too small and
too transient--held together by very weak molecular
interactions--to be viewed with a light microscope," said Erin
Sheets, a Penn State assistant professor of chemistry who also
is a leader of the project. "To overcome this challenge,"
added Heikal, "we used a combination of imaging and
spectroscopy techniques that we are developing in our
laboratories.
In their experiment, the researchers first labeled the cell
membrane and IgE antibodies with two different fluorescent
tags. Next, they introduced an allergen and watched as it
bound to receptors on the cell membrane, thus initiating an
allergic response.
But to demonstrate that this activity was taking place
within the lipid domain, the researchers had to take
advantage of a property of fluorescence, called fluorescence
lifetime, in which molecules are excited with very short
laser pulses. The length of time a molecule remains in its
excited state before emitting a photon--the fluorescence
lifetime--provides unique information about the
fluorescently-labeled molecule's environment and its
chemical structure. For example, a particular molecule might
relax to its lowest-energy state quickly or slowly depending
on whether it is exposed to a solvent.
Click on image for high-resolution file.
Image courtesy of Erin Sheets, Penn State
Nanostructural changes in the plasma membrane occur upon
antigen stimulation. "We previously showed that our
fluorescently-labeled membrane probe has a longer lifetime
within a cholesterol-rich lipid domain," said Sheets. "Here we
show that changes in this lifetime follow the changes that
occur during the first steps in the allergic response process.
Our results also show that lipid domains in the cell membrane
associate with IgE antibodies and their receptors in the
initial stages of an allergic reaction."
In the future, Sheets and Heikal plan to apply the team's
discoveries to a project involving aging. During the aging
process, T cells, which protect the body from foreign
substances like viruses and cancer cells, can lose their
ability to signal effectively. Sheets and Heikal plan to use
these fluorescence-lifetime imaging tools to examine the
structure and integrity of T-cell membranes with a goal of
determining why they lose their knack for signalling and how
this problem can be corrected.
"We want to compare the effectiveness of signaling in young T
cells, which clear out debris quickly, to old T cells, which
are not as efficient," said Sheets. "I think it will be a
pretty cool application of our technique."
Other Penn State scientists who contributed to this research
include Angel Davey and Keith Krise, both Ph.D. students in
the Department of Chemistry. The work was funded by Penn
State, the National Science Foundation, the Commonwealth of
Pennsylvania, the American Chemical Society, and the National
Institutes of Health.
[ SD L ]
CONTACTS:
Erin Sheets: (+1) 814-863-0044, eds11@psu.edu Ahmed Heikal:
(+1) 814-865-8093, aah12@psu.edu Barbara Kennedy (PIO): (+1)
814-863-4682, science@psu.edu
--------------------------
So what **difference** would there BE in the processing of the
hops .. "hop water extraction (HWE) has anti-allergic effects
" .. and .. "this activity was not observed for the hot water
extract from the hops." .. ?
'Something' is .. missing .. and that something is the
inhibitor of the allergic response .. LOST .. to the process
of extraction .. to 'heat' .. ?
Presentation Number: 191-18 Abstract Division: Nutraceuticals
and Functional Foods Presentation Start/End Time: Tuesday, Jul
31, 2007, 2:00 PM - 5:30 PM Author Information: Yoshihisa
Wakita, Frontier Laboratories of Value Creation, Sapporo
breweries LTD., Yaizu, Japan; Yoshihiro Takata, Frontier
Laboratories of Value Creation, Sapporo breweries LTD., Yaizu,
Japan; Syuuichi Segawa, Frontier Laboratories of Value
Creation, Sapporo breweries LTD., Yaizu, Japan; Yasukazu
Nakakita, Frontier Laboratories of Value Creation, Sapporo
breweries LTD., Yaizu, Japan; Hirotaka Kaneda, Frontier
Laboratories of Value Creation, Sapporo breweries LTD., Yaizu,
Japan; Junji Watari, Frontier Laboratories of Value Creation,
Sapporo breweries LTD., Yaizu, Japan; Tatsuko Enomoto, Enomoto
ENT Clinic, Wakayama, Japan; Tadao Enomoto, Japanese Red Cross
Society, Wakayama Medical Center, Wakayama, Japan Abstract:
Hops (Humulus lupulus L.) are used in the brewing of beer and
are available throughout the world. During evaluation of the
physiological functions of hops, it was shown that hop water
extraction (HWE) has anti-allergic effects in vitro and in
vivo. HWE suppressed histamine release from the human
basophilic KU812 cells; however, this activity was not
observed for the hot water extract from the hops. An oral dose
of 500 mg/kg of HWE significantly inhibited vascular
permeability induced by the intradermal injection of compound
48/80 in ICR mice. This study also tested the effect of HWE in
the treatment of seasonal allergic rhinitis during the
major season of this allergy in Japan. In a 12-week
randomized, double-blind, placebo- controlled clinical
trial, patients with seasonal allergic rhinitis were given
100mg of HWE (n=20) or placebo (n=19) per day. The three
nasal symptoms (sneezing, runny nose and stuffiness) and
one non- nasal symptom (hindrance to daily life) were
scored using a 5-point scale daily: 0, absent; 1, mild; 2,
moderate; 3, severe; and 4, very severe. The total symptom
scores were calculated from the sum of the above 4 symptom
scores per week and changes of those between the first week
and each week were calculated. During the trial period, the
elevation of symptom scores was observed as the dispersion
of pollen in the trial area. However, after 10 weeks, the
patients of the HWE group showed significantly lower
changes of total symptom scores from the first week
compared to the placebo group (P<0.05). Thus, HWE is an
effective foodstuff for the improvement of the quality of
life for patients with seasonal allergic rhinitis, and
would be easily applied to beverages.
-------------------------
J Agric Food Chem. 2007 Oct 31;55(22):9054-8. Epub 2007 Oct
10. Links Effects of phytic Acid on peanut allergens and
allergenic properties of extracts. Chung SY, Champagne ET.
sych...@srrc.ars.usda.gov.
Phytic acid would form soluble and insoluble complexes with
proteins. Our objective was to determine if phytic acid forms
insoluble complexes with major peanut allergens, and if such
reaction results in a peanut extract with a lower level of
soluble allergens and allergenic property. Extracts from raw
and roasted peanuts were treated with and without phytic acid
at various pH values and then analyzed by SDS-PAGE and a
competitive inhibition ELISA (ciELISA). The ciELISA measured
IgE binding using a pooled serum from peanut- allergic
individuals. Results showed that phytic acid formed complexes
with the major peanut allergens (Ara h 1 and Ara h 2), which
were insoluble in acidic and neutral conditions. Succinylation
of the allergens inhibited complex formation, indicating that
lysine residues were involved. A 6-fold reduction in IgE
binding or allergenic potency of the extract was observed
after treatment with phytic acid. It was concluded that phytic
acid formed insoluble complexes with the major peanut
allergens, and resulted in a peanut extract with reduced
allergenic potency. Application of phytic acid to a peanut
butter slurry presented a similar result, indicating that
phytic acid may find use in the development of hypoallergenic
peanut-based products.
PMID: 17927201 [PubMed - in process]
Who loves ya. Tom
Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com
Man Is A Herbivore! http://tinyurl.com/a3cc3
DEAD PEOPLE WALKING http://tinyurl.com/zk9fk
7 March 2008--A team of Penn State University researchers is
the first to demonstrate that lipid molecules in cell
membranes participate in mammals' reactions to allergens in a
living cell. The finding will help scientists better
understand how allergy symptoms are triggered, and could
contribute to the creation of improved drugs to treat them.
The work will be reported in the 14 March issue of the Journal
of Biological Chemistry.
The team studied clusters of cholesterol-rich lipid molecules
that they believe serve as platforms for the receptors that
receive antibodies, the proteins that protect the body from
allergens. In this case, the team examined IgE antibodies,
which upon binding to their receptors initiate a cell's
release of histamine--the substance that causes the
unpleasant, but beneficial, mucous production, congestion, and
itchiness associated with allergies. "This research is
basically the molecular foundation for why many people sneeze
in the spring," said Ahmed Heikal, an associate professor in
the Department of Bioengineering and a leader of the project.
While the idea that lipid clusters--also known as lipid
domains--are involved in the allergic response is not new, the
Penn State team is the first to document this connection in a
living cell under physiological conditions. "No one has
observed the domains in action because they are too small and
too transient--held together by very weak molecular
interactions--to be viewed with a light microscope," said Erin
Sheets, a Penn State assistant professor of chemistry who also
is a leader of the project. "To overcome this challenge,"
added Heikal, "we used a combination of imaging and
spectroscopy techniques that we are developing in our
laboratories.
In their experiment, the researchers first labeled the cell
membrane and IgE antibodies with two different fluorescent
tags. Next, they introduced an allergen and watched as it
bound to receptors on the cell membrane, thus initiating an
allergic response.
But to demonstrate that this activity was taking place
within the lipid domain, the researchers had to take
advantage of a property of fluorescence, called fluorescence
lifetime, in which molecules are excited with very short
laser pulses. The length of time a molecule remains in its
excited state before emitting a photon--the fluorescence
lifetime--provides unique information about the
fluorescently-labeled molecule's environment and its
chemical structure. For example, a particular molecule might
relax to its lowest-energy state quickly or slowly depending
on whether it is exposed to a solvent.
Click on image for high-resolution file.
Image courtesy of Erin Sheets, Penn State
Nanostructural changes in the plasma membrane occur upon
antigen stimulation. "We previously showed that our
fluorescently-labeled membrane probe has a longer lifetime
within a cholesterol-rich lipid domain," said Sheets. "Here we
show that changes in this lifetime follow the changes that
occur during the first steps in the allergic response process.
Our results also show that lipid domains in the cell membrane
associate with IgE antibodies and their receptors in the
initial stages of an allergic reaction."
In the future, Sheets and Heikal plan to apply the team's
discoveries to a project involving aging. During the aging
process, T cells, which protect the body from foreign
substances like viruses and cancer cells, can lose their
ability to signal effectively. Sheets and Heikal plan to use
these fluorescence-lifetime imaging tools to examine the
structure and integrity of T-cell membranes with a goal of
determining why they lose their knack for signalling and how
this problem can be corrected.
"We want to compare the effectiveness of signaling in young T
cells, which clear out debris quickly, to old T cells, which
are not as efficient," said Sheets. "I think it will be a
pretty cool application of our technique."
Other Penn State scientists who contributed to this research
include Angel Davey and Keith Krise, both Ph.D. students in
the Department of Chemistry. The work was funded by Penn
State, the National Science Foundation, the Commonwealth of
Pennsylvania, the American Chemical Society, and the National
Institutes of Health.
[ SD L ]
CONTACTS:
Erin Sheets: (+1) 814-863-0044, eds11@psu.edu Ahmed Heikal:
(+1) 814-865-8093, aah12@psu.edu Barbara Kennedy (PIO): (+1)
814-863-4682, science@psu.edu
--------------------------
So what **difference** would there BE in the processing of the
hops .. "hop water extraction (HWE) has anti-allergic effects
" .. and .. "this activity was not observed for the hot water
extract from the hops." .. ?
'Something' is .. missing .. and that something is the
inhibitor of the allergic response .. LOST .. to the process
of extraction .. to 'heat' .. ?
Presentation Number: 191-18 Abstract Division: Nutraceuticals
and Functional Foods Presentation Start/End Time: Tuesday, Jul
31, 2007, 2:00 PM - 5:30 PM Author Information: Yoshihisa
Wakita, Frontier Laboratories of Value Creation, Sapporo
breweries LTD., Yaizu, Japan; Yoshihiro Takata, Frontier
Laboratories of Value Creation, Sapporo breweries LTD., Yaizu,
Japan; Syuuichi Segawa, Frontier Laboratories of Value
Creation, Sapporo breweries LTD., Yaizu, Japan; Yasukazu
Nakakita, Frontier Laboratories of Value Creation, Sapporo
breweries LTD., Yaizu, Japan; Hirotaka Kaneda, Frontier
Laboratories of Value Creation, Sapporo breweries LTD., Yaizu,
Japan; Junji Watari, Frontier Laboratories of Value Creation,
Sapporo breweries LTD., Yaizu, Japan; Tatsuko Enomoto, Enomoto
ENT Clinic, Wakayama, Japan; Tadao Enomoto, Japanese Red Cross
Society, Wakayama Medical Center, Wakayama, Japan Abstract:
Hops (Humulus lupulus L.) are used in the brewing of beer and
are available throughout the world. During evaluation of the
physiological functions of hops, it was shown that hop water
extraction (HWE) has anti-allergic effects in vitro and in
vivo. HWE suppressed histamine release from the human
basophilic KU812 cells; however, this activity was not
observed for the hot water extract from the hops. An oral dose
of 500 mg/kg of HWE significantly inhibited vascular
permeability induced by the intradermal injection of compound
48/80 in ICR mice. This study also tested the effect of HWE in
the treatment of seasonal allergic rhinitis during the
major season of this allergy in Japan. In a 12-week
randomized, double-blind, placebo- controlled clinical
trial, patients with seasonal allergic rhinitis were given
100mg of HWE (n=20) or placebo (n=19) per day. The three
nasal symptoms (sneezing, runny nose and stuffiness) and
one non- nasal symptom (hindrance to daily life) were
scored using a 5-point scale daily: 0, absent; 1, mild; 2,
moderate; 3, severe; and 4, very severe. The total symptom
scores were calculated from the sum of the above 4 symptom
scores per week and changes of those between the first week
and each week were calculated. During the trial period, the
elevation of symptom scores was observed as the dispersion
of pollen in the trial area. However, after 10 weeks, the
patients of the HWE group showed significantly lower
changes of total symptom scores from the first week
compared to the placebo group (P<0.05). Thus, HWE is an
effective foodstuff for the improvement of the quality of
life for patients with seasonal allergic rhinitis, and
would be easily applied to beverages.
-------------------------
J Agric Food Chem. 2007 Oct 31;55(22):9054-8. Epub 2007 Oct
10. Links Effects of phytic Acid on peanut allergens and
allergenic properties of extracts. Chung SY, Champagne ET.
sych...@srrc.ars.usda.gov.
Phytic acid would form soluble and insoluble complexes with
proteins. Our objective was to determine if phytic acid forms
insoluble complexes with major peanut allergens, and if such
reaction results in a peanut extract with a lower level of
soluble allergens and allergenic property. Extracts from raw
and roasted peanuts were treated with and without phytic acid
at various pH values and then analyzed by SDS-PAGE and a
competitive inhibition ELISA (ciELISA). The ciELISA measured
IgE binding using a pooled serum from peanut- allergic
individuals. Results showed that phytic acid formed complexes
with the major peanut allergens (Ara h 1 and Ara h 2), which
were insoluble in acidic and neutral conditions. Succinylation
of the allergens inhibited complex formation, indicating that
lysine residues were involved. A 6-fold reduction in IgE
binding or allergenic potency of the extract was observed
after treatment with phytic acid. It was concluded that phytic
acid formed insoluble complexes with the major peanut
allergens, and resulted in a peanut extract with reduced
allergenic potency. Application of phytic acid to a peanut
butter slurry presented a similar result, indicating that
phytic acid may find use in the development of hypoallergenic
peanut-based products.
PMID: 17927201 [PubMed - in process]
Who loves ya. Tom
Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com
Man Is A Herbivore! http://tinyurl.com/a3cc3
DEAD PEOPLE WALKING http://tinyurl.com/zk9fk