Von Willebrand factor & Complement with LPS and Lectin or Selectin -- Blood Clots or Cardio Pathway or skin Monkey Business with Psoriasis?

[randall]

hi


Complement and Von Willebrand factor in PSORIASIS WOUND sites or any
OLD or NEW wound site.


4 hits : Von Willebrand factor (vWF) - pn g
https://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&q=Von+Willebrand+factor&start=0&hl=en&

we have 241 hits for : complement - p ng (think LPS )
https://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&q=complement&start=0&hl=en&


16 of 241 have C3 - p ng
https://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&group=alt.support.skin-diseases.psoriasis&q=complement+c3&qt_g=Search+this+group

10 of 241 have C3A - p ng
https://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&group=alt.support.skin-diseases.psoriasis&q=complement+c3a&qt_g=Search+this+group

23 of 241 hits have : C5A
https://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&q=complement+c5a&start=0&scoring=d&hl=en&

ONLY seven have C5 + complement.

OK


Why is it important?

Because when JXR aka JRStern put the good article from XOMA on this
site it made more sense then anything else at the time.

So read it on this group. Simply use :good article silverman xoma,
iirc.


http://en.wikipedia.org/wiki/Complement_system
The complement system helps or “complements” the ability of antibodies
and phagocytic cells to clear pathogens from an organism. It is part
of the immune system called the innate immune system[1] that is not
adaptable and does not change over the course of an individual's
lifetime. However, it can be recruited and brought into action by the
adaptive immune system.

The complement system consists of a number of small proteins found in
the blood, generally synthesized by the liver, and normally
circulating as inactive precursors (pro-proteins). When stimulated by
one of several triggers, proteases in the system cleave specific
proteins to release cytokines and initiate an amplifying cascade of
further cleavages. The end-result of this activation cascade is
massive amplification of the response and activation of the cell-
killing membrane attack complex. Over 25 proteins and protein
fragments make up the complement system, including serum proteins,
serosal proteins, and cell membrane receptors. They account for about
5% of the globulin fraction of blood serum.

Three biochemical pathways activate the complement system: the
classical complement pathway, the alternative complement pathway, and
the lectin pathway.[2]
<snip>

http://en.wikipedia.org/wiki/Alternative_complement_pathway
image or diagram if you wish:
http://upload.wikimedia.org/wikipedia/commons/0/0b/Complement_pathway.png
or
http://upload.wikimedia.org/wikipedia/commons/b/b0/Complement-pathways.png

http://en.wikipedia.org/wiki/Lectin_pathway

157 hits : lectin - p ng
https://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&q=lectin&start=0&hl=en&

141 of 157 have keyword: pathway - p ng
https://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&q=lectin&start=0&hl=en&


http://en.wikipedia.org/wiki/Complement_component_5


http://www.sciencedaily.com/releases/2013/04/130401111547.htm
Link Between Blood Clotting, Immune Response Uncovered

Apr. 1, 2013 — Rice University researchers have found an unexpected
link between a protein that triggers the formation of blood clots and
other proteins that are essential for the body's immune system. The
find could lead to new treatments for thousands of patients who suffer
from inflammatory diseases and disorders that cause abnormal blood
clotting.

The research is available online in the journal PLOS ONE.

"This link opens the door for studying severe, debilitating
inflammatory disorders where the disease mechanism is still poorly
understood, including lupus, rheumatoid arthritis, regional ileitis
and ulcerative colitis, as well as age-related macular degeneration,"
said study co-author Dr. Joel Moake, a hematologist and senior
research scientist in bioengineering at Rice. "There's clinical
evidence that clotting and inflammation are somehow linked in many
patients, even in the absence of an infection. This linkage could help
explain some of the clinical cases that have long baffled physicians."

The link is biochemical. Nancy Turner, a research technician in
Moake's lab, established the link after conducting hundreds of
experiments on more than a dozen proteins, including key molecules
involved with both clotting and the body's innate immune response.

"In addition to the clinical evidence, there's also a logical basis
for this connection," Moake said. "Clotting is a type of wound
response, and wounds are magnets for infection, so there could be a
selective advantage in triggering both responses at the same time."

But the link could also have a downside. For example, if a person has
a genetic mutation or acquired disorder that causes their blood to
clot more often or more extensively than normal, the overactive
clotting could lead to the kind of inflammation that would typically
be caused by an infection. Furthermore, initiation of the clotting
process may initiate clinical relapses in patients susceptible to
various types of severe inflammatory disease.

In fact, the symptoms in the above scenarios are not uncommon. For
example, in prior research, Moake's lab conducted pioneering research
on two disorders: thrombotic thrombocytopenic purpura (TTP), which
causes clots to form in small blood vessels throughout the body; and
hemolytic uremic syndrome (HUS), which causes abnormal blood clots in
the kidneys. Both HUS and TTP come in two varieties -- one that is
triggered by infection or inappropriate antibody formation, and
another that is hereditary. Moake said the newfound link between clot
formation and the immune response could help improve the diagnosis and
treatment for TTP, HUS and other puzzling blood disorders with similar
symptoms.

The experiments Turner used to establish the link between clotting and
the body's immune response involved a key clotting protein called von
Willebrand factor (VWF) and about a dozen other proteins that are
components of the "complement system." The complement system, a part
of the body's innate immune system, is one of biology's most ancient
forms of defense against invading pathogens.

The complement system consists of a series of proteins that are
produced by a variety of cell types. These proteins circulate
continuously in the bloodstream and react sequentially upon
activation. When triggered, the complement component proteins join
together to form a biological weapon called the "membrane attack
complex" (MAC), which kills both invading bacteria and the body's own
cells if they become infected or damaged.

Turner and Moake first thought of looking for the link more than two
years ago after they collaborated with physicians at Texas Children's
Hospital on several puzzling clinical cases. Turner designed and
conducted a series of experiments to examine whether any of the
proteins in the complement complex were likely to bind onto long
strands of VWF. Each complement protein was detected with a specific
antibody and a fluorescent tag that could be viewed with a specialized
microscope.

She found that C3, an important complement pathway initiator protein,
was produced by cells in such low concentration that it was almost
impossible to see -- even with a fluorescent microscope. But that
changed when she looked at experimental samples that contained both C3
and VWF.

"The signals were so clear," Turner recalled. "The VWF had so much C3
on it that it looked like a Christmas tree."

Moake said he and Turner are conducting follow-up research to measure
more effectively the activation of C3 on VWF. They are also measuring
whether the C3 activation stimulates the sequential cascade of
reactions that leads to MAC formation. In particular, they are
interested in studying how the connection might lead to autoimmune
diseases by causing MAC to target the body's own healthy cells rather
than sick or damaged cells.

"We'd like to know what happens on a cell's surface that ordinarily
enables it to protect itself against MAC," Moake said. "We'd also like
to know what can go wrong with cells in terms of sickness or trauma
that might make them more susceptible to being attacked and killed by
overactivation of the complement sequence during clotting."
<snip>

http://en.wikipedia.org/wiki/Complement_membrane_attack_complex
The membrane attack complex (MAC) is typically formed on the surface
of pathogenic bacterial cells as a result of the activation of the
alternative pathway and the classical pathway of the complement
system, and it is one of the effector proteins of the immune system.
The membrane-attack complex (MAC) forms transmembrane channels. These
channels disrupt the phospholipid bilayer of target cells, leading to
cell lysis and death
<snip>

http://en.wikipedia.org/wiki/Von_Willebrand_factor
Von Willebrand factor (vWF) is a blood glycoprotein involved in
hemostasis. It is deficient or defective in von Willebrand disease and
is involved in a large number of other diseases, including thrombotic
thrombocytopenic purpura, Heyde's syndrome, and possibly hemolytic-
uremic syndrome.[1] Increased plasma levels in a large number of
cardiovascular, neoplastic, and connective tissue diseases are
presumed to arise from adverse changes to the endothelium, and may
contribute to an increased risk of thrombosis

http://en.wikipedia.org/wiki/Von_Willebrand_factor#Role_in_disease

Journal Reference for article (no pmid # yet):
Nancy A. Turner, Joel Moake. Assembly and Activation of Alternative
Complement Components on Endothelial Cell-Anchored Ultra-Large Von
Willebrand Factor Links Complement and Hemostasis-Thrombosis. PLoS
ONE, 2013; 8 (3): e59372 DOI: 10.1371/journal.pone.0059372

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0059372
Assembly and Activation of Alternative Complement Components on
Endothelial Cell-Anchored Ultra-Large Von Willebrand Factor Links
Complement and Hemostasis-Thrombosis
Nancy A. Turner -- Joel Moake

Abstract
Background
Vascular endothelial cells (ECs) express and release protein
components of the complement pathways, as well as secreting and
anchoring ultra-large von Willebrand factor (ULVWF) multimers in long
string-like structures that initiate platelet adhesion during
hemostasis and thrombosis. The alternative complement pathway (AP) is
an important non-antibody-requiring host defense system. Thrombotic
microangiopathies can be associated with defective regulation of the
AP (atypical hemolytic-uremic syndrome) or with inadequate cleavage by
ADAMTS-13 of ULVWF multimeric strings secreted by/anchored to ECs
(thrombotic thrombocytopenic purpura). Our goal was to determine if EC-
anchored ULVWF strings caused the assembly and activation of AP
components, thereby linking two essential defense mechanisms.

Methodology/Principal Findings
We quantified gene expression of these complement components in
cultured human umbilical vein endothelial cells (HUVECs) by real-time
PCR: C3 and C5; complement factor (CF) B, CFD, CFP, CFH and CFI of the
AP; and C4 of the classical and lectin (but not alternative)
complement pathways. We used fluorescent microscopy, monospecific
antibodies against complement components, fluorescent secondary
antibodies, and the analysis of >150 images to quantify the attachment
of HUVEC-released complement proteins to ULVWF strings secreted by,
and anchored to, the HUVECs (under conditions of ADAMTS-13
inhibition). We found that HUVEC-released C4 did not attach to ULVWF
strings, ruling out activation of the classical and lectin pathways by
the strings. In contrast, C3, FB, FD, FP and C5, FH and FI attached to
ULVWF strings in quantitative patterns consistent with assembly of the
AP components into active complexes. This was verified when non-
functional FB blocked the formation of AP C3 convertase complexes
(C3bBb) on ULVWF strings.

Conclusions/Significance
AP components are assembled and activated on EC-secreted/anchored
ULVWF multimeric strings. Our findings provide one possible molecular
mechanism for clinical linkage between different types of thrombotic
and complement-mediated disorders.
<snip>

23 hits for : moake + turner -pubmed
http://www.ncbi.nlm.nih.gov/pubmed/?term=moake+turner

23 of 23 have : moake turner + Von Willebrand factor -pubmed
http://www.ncbi.nlm.nih.gov/pubmed/?term=moake+turner+Von+Willebrand+factor

14 hits : psoria* + vWF -pubmed
http://www.ncbi.nlm.nih.gov/pubmed/?term=psoria*+Von+Willebrand+factor


#1 of 12 is from last year:

http://www.ncbi.nlm.nih.gov/pubmed/22882471
J Eur Acad Dermatol Venereol. 2012 Aug 7. doi: 10.1111/j.
1468-3083.2012.04671.x. [Epub ahead of print]
Increased number of circulating endothelial cells (CECs) in patients
with psoriasis - preliminary report.

Batycka-Baran A, Paprocka M, Krawczenko A, Duś D, Szepietowski JC.

Source
Department of Dermatology, Venereology and Allergology Wroclaw Medical
University, Chalubinskiego, Wroclaw, Poland Institute of Immunology
and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla,
Wroclaw, Poland.

Abstract
Background  Numerous studies have demonstrated increased
cardiovascular risk in psoriasis. Circulating endothelial cells (CECs)
have been proposed as a new marker of endothelial dysfunction that
plays an important role in pathogenesis of atherosclerosis. Objective
The aim of this study was to compare the number of CECs in psoriatic
patients to a control group and to analyze possible correlations
between the numbers of CECs and the plasma levels of classical markers
of endothelial dysfunction, such as: sICAM-1, sE-selectin and von
Willebrand factor (vWF). Methods  The number of CECs, identified as
CD146 + / CD45- cells, were determined in peripheral blood with using
flow cytometry in psoriatic patients (n = 63) and controls (n = 31).
The plasma levels of: sICAM-1, sE-selectin, vWF were measured with
ELISA. The severity of psoriasis was assessed with PASI. Results  The
number of CECs was significantly increased in psoriatic patients
compared with controls (P < 0.00001) and positively correlated with
disease severity (R = 0.360; P = 0.0037). The levels of sICAM-1, sE-
selectin and vWF were significantly elevated in psoriatic patients (P
< 0.00001; P < 0.00001; P = 0.00072, respectively). The number of CECs
was significantly, positively correlated with the levels of sICAM-1 (R
= 0.393; P = 0.0014) and vWF (R = 0.314; P = 0.012) in psoriatic
patients. The levels of sICAM-1 and sE-selectin were positively
correlated with disease severity (R = 0.356; P = 0.0041 and R = 0.407;
P = 0.0009, respectively). Conclusion  The increased number of CECs
that correlates with disease severity and plasma levels of sICAM-1 and
vWF may indicate endothelial dysfunction or injury in patients with
psoriasis.

PMID: 22882471 <this one has been posted on the p ng>

here:
https://groups.google.com/group/alt.support.skin-diseases.psoriasis/msg/1bfb737d8c71b991?hl=en&&q=Von+Willebrand+factor
another vWF is : PMID: 20703838
Here:
https://groups.google.com/group/alt.support.skin-diseases.psoriasis/msg/456db53a1b1e0195?hl=en&&q=Von+Willebrand+factor

291 hits : complement Von Willebrand factor- pubmed
http://www.ncbi.nlm.nih.gov/pubmed/?term=complement+Von+Willebrand+factor

And since we've got leaky guts: LPS + above 291 hits = 4 hits
http://www.ncbi.nlm.nih.gov/pubmed/?term=complement+Von+Willebrand+factor+lps

And still ONLY 63 hits dropping complement: vWF + LPS -pubmed
http://www.ncbi.nlm.nih.gov/pubmed/?term=Von+Willebrand+factor+lps


#1 of 63 makes more sense then the japanese sea cucumber #1 of 4.


http://www.ncbi.nlm.nih.gov/pubmed/22871409
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2012 Aug;24(8):487-9.
[The effects of activated protein C on the von Willebrand factor and
von Willebrand factor cleaving protease of rat aortic endothelial cell
induced by lipopolysaccharide].

Zheng GJ, Wu ZX, Zhu HY, Yin DM, Sun Q, Li YP.

Source
Department of Critical Care Medicine, Zhuozhou City Hospital of Hebei
Province, Zhuozhou, Hebei, China.

Abstract
OBJECTIVE:
To investigate the activated protein C (APC) on the von Willebrand
factor antigen (vWFAg) and von Willebrand factor cleaving protease
(ADAMTS-13) protein expression in rat aortic endothelial cells (RAECs)
induced by lipopolysaccharide (LPS).

METHODS:
RAECs from Wistar rats were cultured with the tissue explants
adherence method. RAECs were cultured for one week, After one week
culture, RAECs in 4-5 generations were divided into control group, LPS
stimulation groups (1 mg/L) and APC intervention groups (0.1, 1 and 10
mg/L APC was added after LPS stimulation). The supernatants were
obtained at 12, 24, 48, and 72 hours after LPS stimulated to determine
the vWFAg and protein of ADAMTS-13 expression by enzyme-linked
immunoadsorbent assay (ELISA).

RESULTS:
In the control group, RAECs expressed little vWFAg and protein of
ADAMTS-13. With stimulation of LPS, the vWFAg was significantly
increased at 12 hours, and reached the peak at 48 hours
[(285.45±30.13)%], and the level of ADAMTS-13 (μg/L) was gradually
decreased, and reached the nadir at 72 hours (13.32±2.37), there was
significant difference compared with control group [vWFAg:
(94.53±7.83)%, ADAMTS-13: 115.76±2.36, both P<0.01). The effects on
vWFAg promoting and ADAMTS-13 inhibition after LPS stimulation could
be dose-dependently reversed by APC. 10 mg/L of APC could decrease the
peak of vWFAg at 48 hours of LPS stimulation [(198.43±17.92)% vs.
(285.45±30.13)%], and increase the minimize of ADAMTS-13 (μg/L) at 72
hours of LPS stimulation (125.25±2.70 vs. 13.32±2.37), with
significant difference (both P<0.01).

CONCLUSIONS:
After stimulation with LPS, the level of vWFAg was time-dependent
increased, as the protein of ADAMTS-13 was decreased. APC could
attenuate the effect of LPS on vWFAg and protein of ADAMTS-13 with
dose-dependent and time-dependent patterns.

PMID: 22871409


and ADAMTS-13 is ...

ADAMTS-13
http://en.wikipedia.org/wiki/ADAMTS13
Symbols ADAMTS13; 13; ADAM-TS; ADAM-TS13; ADAMTS-13; C9orf8; TTP;
VWFCP; vWF-CP
ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin
type 1 motif, member 13)—also known as von Willebrand factor-cleaving
protease (VWFCP)—is a zinc-containing metalloprotease enzyme that
cleaves von Willebrand factor (vWf), a large protein involved in blood
clotting. It is secreted in blood and degrades large vWf multimers,
decreasing their activity.[1]

[...] Role in disease
Deficiency of ADAMTS13 was originally discovered in Upshaw-Schülman
syndrome, the recurring familial form of thrombotic thrombocytopenic
purpura. By that time it was already suspected that TTP occurred in
the autoimmune form as well, owing to its response to plasmapheresis
and characterisation of IgG inhibitors. Since the discovery of
ADAMTS13, specific epitopes on its surface have been shown to be the
target of inhibitory antibodies.[1][2][3]

Especially since the link between aortic valve stenosis and
angiodysplasia was proven to be due to high shear stress (Heyde's
syndrome), it has been accepted that increased exposure of vWf to
ADAMTS13 due to various reasons would predispose to bleeding by
causing increased degradation of vWf. This phenomenon is characterised
by a form of von Willebrand disease (type 2a).[1]
<snip>

1,208 hits : ADAMTS13 - pubmed
ADAMTS13
http://www.ncbi.nlm.nih.gov/pubmed/?term=ADAMTS13

96 of 1208 have : autoimmune
http://www.ncbi.nlm.nih.gov/pubmed/?term=ADAMTS13+autoimmune

six hits of 96 with skin
http://www.ncbi.nlm.nih.gov/pubmed/?term=ADAMTS13+skin


and i'm not seeing anything.. so not holding my breath right NOW..


randall... good luck.. with sodium and pepper and curcumin and
starvation.. LOL try L. plantarum instead.. <w>