1 C1INH also suppressed LPS-induced up-regulation of TNF-a
2 C1INH consists of two distinct domains: a serpin domain
3 C1INH in which N-linked carbohydrate was removed by usin
4 C1INH is the main inhibitor of the contact system.
5 C1INH may be important in protection from sepsis through
6 C1INH sialylated-N- and -O-glycans were not only essenti
7 C1INH-deficient mice (C1INH-/- mice) subjected to CLP ha
8 C1INH-deficient mice showed no obvious phenotypic abnorm
9 Investigators have generated
a C1INH-/- mouse model that has demonstrated the importanc
10 this study, we demonstrated that both
active C1INH and reactive center-cleaved, inactive C1INH protec
11 In
addition,
C1INH was shown to bind to diphosphoryl lipid A (dLPA) b
12 ure model of endothelial-leukocyte
adhesion,
C1INH showed inhibition in a dose-dependent manner.
13 ng to RAW 264.7 cells was reversed with
anti-
C1INH Ab and was more efficient when C1INH was incubated
14 However,
both C1INH and iC1INH enhanced the bactericidal activity of b
15 Mice with deficiency of
both C1INH and Bk2R demonstrated diminished vascular permeabi
16 pond well to modest increases of
circulating C1INH activity levels because inhibition of fluid-phase
17 oth native C1INH and reactive center
cleaved C1INH significantly inhibit selectin-mediated leukocyte
18 Furthermore, reactive-center-
cleaved C1INH attenuated pulmonary damage evoked by intravenous
19 trated by the use of reactive-center-
cleaved C1INH, but dependent on its glycosylation status.
20 Collectively,
C1INH administration provides a new therapeutic option f
21 N-
deglycosylated C1INH also failed to suppress fluorescein isothiocyanate
22 ed immunosorbent assay, the N-
deglycosylated C1INH bound to LPS very poorly.
23 and in vivo models, whereas N-
deglycosylated C1INH loses such activities.
24 with intact LPS, binding of N-
deglycosylated C1INH to dLPA and mLPA was diminished in comparison with
25 (TEE) have been reported with plasma-
derived C1INH, but so far none with recombinant human C1INH (rhC
26 d prophylactic treatment with plasma-
derived C1INH.
27 (C1-INH-HAE) includes therapy with
exogenous C1INH.
28 First,
C1INH bound to glycan moieties within P. falciparum glyc
29 Heterozygosity
for C1INH deficiency results in hereditary angioedema, which
30 s blue dye, both homozygous and
heterozygous C1INH-deficient mice revealed increased vascular permeab
31 In vivo,
histone-
C1INH complexes were detected in bronchoalveolar lavage
32 reversed by treatment with intravenous
human C1INH, with a Kunitz domain plasma kallikrein inhibitor
33 1INH, but so far none with recombinant
human C1INH (rhC1INH).
34 We found that
human C1INH, at therapeutically relevant doses, blocks severe
35 The data suggest that the mutation
in C1INH-Ta results in a folding abnormality that behaves a
36 on because reactive center-cleaved,
inactive C1INH (iC1INH) also was effective.
37 C1INH and reactive center-cleaved,
inactive C1INH protected mice from lethal Gram-negative endotoxem
38 Heterozygosity for C1
inhibitor (
C1INH) deficiency results in hereditary angioedema.
39 Plasma C1
inhibitor (
C1INH) is a natural inhibitor of complement and contact
40 C1
inhibitor (
C1INH) is beneficial in animal models of endotoxemia and
41 C1
inhibitor (
C1INH) prevents endotoxin shock in mice via a direct int
42 The C1
inhibitor (
C1INH) promoter is unusual in two respects: 1) It contai
43 C1
inhibitor (
C1INH) protects mice from lethal Gram-negative bacterial
44 C1
inhibitor (
C1INH), a member of the serine proteinase inhibitor (ser
45 The C1
inhibitor (
C1INH), a plasma complement regulatory protein, prevents
46 Dysfunctional C1
inhibitor (
C1INH)-Ta is a naturally occurring mutant from a patient
47 by a deficiency of functional C1-
inhibitor (
C1INH) becomes clinically manifest as attacks of angioed
48 Human C1-
inhibitor (
C1INH) is a multifunctional protease inhibitor that regu
49 of first component of complement-
inhibitor (
C1INH).
50 Recombinant human C1 esterase
inhibitor (
C1INH) serves as a promising future alternative to curre
51 To explore whether C1 esterase
inhibitor (
C1INH), an endogenous inhibitor of the contact phase, ma
52 Insufficient C1INH activity leads to uncontrolled activation of plasm
53 minal domain, mutations were introduced
into C1INH at the three N-linked glycosylation sites and at t
54 se Factor XIIa and kallikrein requires
lower C1INH levels than inhibition of activator-bound factors.
55 C1INH-deficient
mice (
C1INH-/- mice) subjected to CLP had a higher mortality t
56 Here we show that both
native C1INH and reactive center cleaved C1INH significantly in
57 The ability
of C1INH to control the inflammatory processes was studied
58 Here, we demonstrate that application
of C1INH alleviates bleomycin-induced lung injury via direc
59 In addition, the binding
of C1INH mutants to diphosphoryl lipid A was decreased in c
60 eavily glycosylated amino-terminal domain
of C1INH.
61 as significantly increased with two doses
of C1INH, one given immediately following CLP, and the seco
62 he multifaceted anti-inflammatory effects
of C1INH in various animal models and human diseases.
63 Optimal efficacy
of C1INH therapy is achieved at doses >/=50 U/kg.
64 ent of HAE attacks suggests that efficacy
of C1INH therapy is optimal when C1INH activity levels are
65 mLPA had any effect on the rate or extent
of C1INH complex formation with C1s or on cleavage of the r
66 Both forms
of C1INH blocked the LPS-binding protein-dependent binding
67 a demonstrate that N-linked glycosylation
of C1INH is essential to mediate its interaction with the L
68 Therefore, the interaction
of C1INH with gram-negative bacterial LPS is dependent both
69 The interaction
of C1INH with LPS was directly demonstrated both by ELISA a
70 Direct involvement
of C1INH in modulation of selectin-mediated cell adhesion m
71 The target level
of C1INH activity needed to achieve optimal efficacy, howev
72 We determined the plasma level
of C1INH associated with optimal clinical efficacy in the t
73 However, no multimerization
of C1INH-Ta isolated from serum or of C1INH-Ta in serum, wa
74 The mutation
of C1INH at all four positively charged amino acid residues
75 zation of C1INH-Ta isolated from serum or
of C1INH-Ta in serum, was observed.
76 ract might be important in the regulation
of C1INH promoter activity.
77 However, the mechanism(s)
of C1INH protection remain(s) ill-defined.
78 Survival
of C1INH-/- mice was significantly increased with two doses
79 ation was 1 h with icatibant and 2 h with
pd-
C1INH and median time from drug administration to comple
80 This dose increases
plasma C1INH activity in almost all patients to values >/=0.7 U
81 sent studies test the hypothesis that
plasma C1INH bears sialyl Lewis(x)-related moieties and therefo
82 The data also show that
plasma C1INH can bind to P- and E-selectins by FACS and immunop
83 We demonstrated that
plasma C1INH does express sialyl Lewis(x)-related moieties on i
84 Treatment with
plasma C1INH is effective not only in patients with hereditary
85 Recombinant C1INH-Ta revealed an intermediate thermal stability in c
86 Recombinant C1INH-Ta, on 7.5% SDS-polyacrylamide gel electrophoresis
87 ect of weekly administrations of
recombinant C1INH (rhC1INH).
88 Plasma-derived or
recombinant C1INH products are approved for the treatment of such an
89 AE with either plasma-derived or
recombinant C1INH products, tested at various doses.
90 Second,
C1INH bound to host CD36 and chondroitin sulfate A molec
91 The data support the hypothesis
that C1INH plays a direct role in leukocyte-endothelial cell
92 This study reveals
that C1INH is a potential therapeutic antimalarial molecule a
93 We have shown
that C1INH expresses the sialyl-Lewis(x) tetrasaccharide on i
94 This discovery may suggest
that C1INH plays a role in the endothelial-leukocyte interact
95 The C1INH gene also contains a number of potential regulator
96 The C1INH mutants that did not bind to LPS also did not supp
97 The C1INH-Ta dimer expressed the epitopes that normally are
98 Disruption of
the C1INH gene by gene trapping enabled the generation of ho
99 role of these elements in regulation of
the C1INH promoter was examined.
100 In addition, treatment of
the C1INH-deficient mice with an angiotensin-converting enzy
101 Therefore,
C1INH, in addition to its function as a serine protease
102 omparison with that of recombinant wild-
type C1INH.
103 The differences in half-lives of the
various C1INH products do not have an obvious effect on clinical
104 In
vitro,
C1INH bound to bacteria cultured from blood or peritonea
105 In
vitro,
C1INH was found to bind all histone types.
106 In
vivo,
C1INH and iC1INH both reduced the number of viable bacte
107 th anti-C1INH Ab and was more efficient
when C1INH was incubated first with LPS rather than with the
108 at efficacy of C1INH therapy is optimal
when C1INH activity levels are restored to the normal range.
109 hed vascular permeability in comparison
with C1INH-deficient, Bk2R-sufficient mice.
110 LP) model for sepsis in mice, treatment
with C1INH improved survival in comparison with untreated con
111 Treatment
with C1INH may provide a useful additional therapeutic approa
112 enient acute and prophylactic treatment
with C1INH.