The Effect of Brinase on Fibrinogen in Vivo

1975 ◽  
Vol 33 (02) ◽  
pp. 217-220 ◽  
Author(s):  
D Nyman
Keyword(s):  
Fibrin Polymerization ◽  
Α Chain

SummaryBrinase infusions in man cause, without excessive lowering of the inhibitor capacity, a slowing of the fibrin polymerization. This is combined with a degradation of the A α chain into two major fragments. Both fragments carry crosslinking sites. Brinase infusion also causes positive ethanol gelation. Evidence for the formation of γ dimers was found.

scholarly journals C4b-binding protein α-chain enhances antitumor immunity by facilitating the accumulation of tumor-infiltrating lymphocytes in the tumor microenvironment in pancreatic cancer

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Kosuke Sasaki ◽  
Shigetsugu Takano ◽  
Satoshi Tomizawa ◽  
Yoji Miyahara ◽  
Katsunori Furukawa ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Microenvironment ◽  
Binding Protein ◽  
Combined Treatment ◽  
Tumor Infiltrating Lymphocytes ◽  
Pdac Cell ◽  
Α Chain ◽  
Infiltrating Lymphocytes

Abstract Background Recent studies indicate that complement plays pivotal roles in promoting or suppressing cancer progression. We have previously identified C4b-binding protein α-chain (C4BPA) as a serum biomarker for the early detection of pancreatic ductal adenocarcinoma (PDAC). However, its mechanism of action remains unclear. Here, we elucidated the functional roles of C4BPA in PDAC cells and the tumor microenvironment. Methods We assessed stromal C4BPA, the C4BPA binding partner CD40, and the number of CD8+ tumor-infiltrating lymphocytes in resected human PDAC tissues via immunohistochemical staining. The biological functions of C4BPA were investigated in peripheral blood mononuclear cells (PBMCs) and human PDAC cell lines. Mouse C4BPA (mC4BPA) peptide, which is composed of 30 amino acids from the C-terminus and binds to CD40, was designed for further in vitro and in vivo experiments. In a preclinical experiment, we assessed the efficacy of gemcitabine plus nab-paclitaxel (GnP), dual immune checkpoint blockades (ICBs), and mC4BPA peptide in a mouse orthotopic transplantation model. Results Immunohistochemical analysis revealed that high stromal C4BPA and CD40 was associated with favorable PDAC prognosis (P=0.0005). Stromal C4BPA strongly correlated with the number of CD8+ tumor-infiltrating lymphocytes (P=0.001). In in vitro experiments, flow cytometry revealed that recombinant human C4BPA (rhC4BPA) stimulation increased CD4+ and CD8+ T cell numbers in PBMCs. rhC4BPA also promoted the proliferation of CD40-expressing PDAC cells. By contrast, combined treatment with gemcitabine and rhC4BPA increased PDAC cell apoptosis rate. mC4BPA peptide increased the number of murine T lymphocytes in vitro and the number of CD8+ tumor-infiltrating lymphocytes surrounding PDAC tumors in vivo. In a preclinical study, GnP/ICBs/mC4BPA peptide treatment, but not GnP treatment, led to the accumulation of a greater number of CD8+ T cells in the periphery of PDAC tumors and to greater tumor regression than did control treatment. Conclusions These findings demonstrate that the combination of GnP therapy with C4BPA inhibits PDAC progression by promoting antitumor T cell accumulation in the tumor microenvironment.

scholarly journals Mechanisms imposing the Vβ bias of Vα14 natural killer T cells and consequences for microbial glycolipid recognition

2006 ◽  
Vol 203 (5) ◽  
pp. 1197-1207 ◽  
Author(s):  
Datsen G. Wei ◽  
Shane A. Curran ◽  
Paul B. Savage ◽  
Luc Teyton ◽  
Albert Bendelac
Keyword(s):  
T Cells ◽  
Natural Killer ◽  
Optimal Solution ◽  
Nkt Cells ◽  
Cell Repertoire ◽  
Transgenic Cells ◽  
Α Chain ◽  
Natural Killer T

Mouse and human natural killer T (NKT) cells recognize a restricted set of glycosphingolipids presented by CD1d molecules, including self iGb3 and microbial α-glycuronosylceramides. The importance of the canonical Vα14-Jα18 TCR α chain for antigen recognition by NKT cells is well recognized, but the mechanisms underlying the Vβ8, Vβ7, and Vβ2 bias in mouse have not been explored. To study the influences of thymic selection and the constraints of pairing with Vα14-Jα18, we have created a population of mature T cells expressing Vα14-Jα18 TCR α chain in CD1d-deficient mice and studied its recognition properties in vitro and in vivo. Transgenic cells expressed a diverse Vβ repertoire but their recognition of endogenous ligands and synthetic iGb3 was restricted to the same biased Vβ repertoire as expressed in natural NKT cells. In contrast, α-GalCer, a synthetic homologue of microbial α-glycuronosylceramides, was recognized by a broader set of Vβ chains, including the biased NKT set but also Vβ6, Vβ9, Vβ10, and Vβ14. These surprising findings demonstrate that, whereas Vβ8, Vβ7, and Vβ2 represent the optimal solution for recognition of endogenous ligand, many Vβ chains that are potentially useful for the recognition of foreign lipids fail to be selected in the NKT cell repertoire.

Immunochemical Studies Of Fibrinogen Products Produced During Thrombosis

1981 ◽  
Author(s):  
R E Canfield
Keyword(s):  
Thrombus Formation ◽  
Factor Xiiia ◽  
Fibrinopeptide A ◽  
Terminal Events ◽  
Α Chain

Immunochemical measurement of the products of fibrinogen proteolysis has provided a method to study the terminal events of coagulation that are initiated by thrombin as well as those events associated with the fibrinolytic actions of plasmin. Thrombin releases fibrinopeptide A (FPA) and later fibrinopeptide B (FPB). Immunologic techniques to measure FPA are now well established; determination of FPB is complicated by degradation of the peptide in plasma. Early plasmin cleavage occurs at the NH2-terminal end of the Bβ-chain of fibrinogen yielding Bβ 1-42. This fragment exhibits limited crossreactivity with antisera to FPB. The action of plasmin at this site on fibrin I may play an important role in determining whether thrombin release of FPA ultimately leads to thrombus formation in vivo. Other early plasmin cleavage products arise from the COOH-terminal half of the α-chain. Details concerning the application of these immunochemical measurements to an understanding of the role of thrombin and plasmin-mediated proteolysis of fibrinogen and fibrin will be discussed. In addition, immunochemical attempts to detect the presence of factor XIIIa-catalyzed crosslinks will also be described.

Inhibition of Fibrin Monomer Polymerization by Lambda Myeloma Globulins

Blood ◽  
1972 ◽  
Vol 39 (2) ◽  
pp. 210-223 ◽  
Author(s):  
Morton Coleman ◽  
Edward M. Vigliano ◽  
Marc E. Weksler ◽  
Ralph L. Nachman
Keyword(s):  
Anticoagulant Activity ◽  
Enzymatic Digestion ◽  
Thrombin Time ◽  
Clot Retraction ◽  
Fibrin Polymerization ◽  
Myeloma Proteins ◽  
Fibrin Monomer ◽  
Low Concentrations ◽  
Polypeptide Chains

Abstract Blood obtained from seven patients with lambda type myeloma proteins showed evidence of gelatinous bulky clots, impaired clot retraction, and circulating anticoagulant activity associated with interference of fibrin monomer polymerization. Five patients had γG1 and two had γA1 myeloma proteins. The pathologic plasmas and isolated myeloma proteins had anticoagulant activity that prolonged both thrombin and reptilase times, that was not absorbed by BaSO4 or neutralized by protamine sulfate, and that resisted heating to 56°C for 10 min. Addition of excess calcium partially corrected the anticoagulant effect. The anticoagulant activity of the isolated whole myeloma proteins, the enzymatic fragments, and polypeptide chains was measured by a thrombin time assay and a spectophotometric system with fibrin monomer. Low concentrations of the isolated IgGL proteins inhibited fibrin polymerization. The IgAL proteins did not demonstrate this activity at low concentrations but were active at concentrations comparable to in vivo levels. F(ab')2 and Fab fragments produced from the IgG proteins by enzymatic digestion possessed full inhibitory activity of the native intact proteins. Fc fragments and isolated polypeptide chains did not display significant anticoagulant activity. The results suggest that the Fab sites of certain lambda myeloma proteins may bind to fibrin during clotting and fibrin polymerization.

Fibrinogen α-Chain Resistance to Arvin (Ancrod) in DIC

1975 ◽  
Author(s):  
R. S. Lane ◽  
O. H. Baugh ◽  
P. T. Flude
Keyword(s):  
Molecular Weight ◽  
Aortic Dissection ◽  
Dissecting Aneurysm ◽  
Plasma Fibrinogen ◽  
Low Molecular Weight ◽  
Fibrin Polymerization ◽  
Rapid Isolation ◽  
Α Chain ◽  
High Concentrations ◽  
Marked Resistance

In high concentrations, Arvin (Ancrod) splits fibrinogen α-chains into fragments of 39,000 and 31,000 molecular weight. In a patient with mild chronic DIC, secondary to a dissecting aneurysm, plasma fibrinogen exhibited marked resistance to normal α-chain proteolysis by Arvin. The patient showed a moderate haemostatic defect acquired from the time of aortic dissection: bleeding was stopped with EACA. Tests were consistent with the presence in plasma of high and low molecular weight FDP, thus deficient haemostasis could be explained by defective fibrin polymerization and X-linking.The α-chain resistance to Arvin was a coincidental finding. Does this behaviour represent a defect and, if so, is it congenital, or acquired representing a previously unencountered phenomenon associated with DIG? The data show Arvin to be a valuable agent for the rapid isolation and investigation of fibrinogen in normal and pathological plasmas.

scholarly journals In vivo regulation of the allergic response by the IL-4 receptor α chain immunoreceptor tyrosine-based inhibitory motif

2010 ◽  
Vol 125 (5) ◽  
pp. 1128-1136.e8 ◽  
Author(s):  
Raffi Tachdjian ◽  
Shadi Al Khatib ◽  
Andreas Schwinglshackl ◽  
Hong Sook Kim ◽  
Andrew Chen ◽  
...  
Keyword(s):  
Allergic Response ◽  
Α Chain

scholarly journals Influence of the Length of the Lipooligosaccharide α Chain on Its Sialylation in Neisseria meningitidis

2002 ◽  
Vol 70 (1) ◽  
pp. 407-411 ◽  
Author(s):  
Chao-Ming Tsai ◽  
George Kao ◽  
Peixuan Zhu
Keyword(s):  
Neisseria Meningitidis ◽  
Human Serum ◽  
Steric Hindrance ◽  
Normal Human Serum ◽  
Normal Human ◽  
Α Chain

ABSTRACT The sialylation of lipooligosaccharide (LOS) in Neisseria meningitidis plays a role in the resistance of the organism to killing by normal human serum. The length of the α chain extending out from the heptose I [Hep (I)] moiety of LOS influenced sialylation of N. meningitidis LOS in vitro and in vivo. The α chain required a terminal Gal and a trisaccharide or longer oligosaccharide to serve as an acceptor for sialylation. The disaccharide lactose (Galβ1-4Glc) in the α chain of immunotype L8 LOS could not function as an acceptor for the sialyltransferase, probably due to steric hindrance imposed by the neighboring Hep (II) with phosphorylethanolamine and another group attached.

Clinical Thrombosis. A Subunit Study of the Fibrin

1975 ◽  
Author(s):  
G. J. L. Strachau ◽  
P. J. Gaffney
Keyword(s):  
Surgical Intervention ◽  
Structural Features ◽  
In Vitro Systems ◽  
A Subunit ◽  
Α Chain ◽  
Polypeptide Chains ◽  
D Dimer ◽  
Made In

The fibrins in venous and arterial thrombi, obtained by surgical intervention, were examined with respect to their subunit compositions. All the fibrin samples examined were totally crosslinked by the action of Factor XIII, e.g. the α chains were crosslinked as α chain polymers (αP) and the γ chains were crosslinked as γ chain dimers (γ-γ), while the β chains were uncrosslinked. The only difference between the subunits of the in vivo formed fibrins and those of in vitro plasma clots, was the consistent presence of some partly digested fibrin chains (of molecular weight 33,000) which were fragments of the β or γ chains, suggesting that the latter polypeptide chains may be more subject to lysis in vivo than the crosslinked α chains. The α chain polymers may be structural features stabilising the thrombus fibrin in vivo.Brinase (a purified extract of Aspergillus Oryzae) was shown in vitro to rapidly lyse the in vivo formed thrombi, having the unique property of degrading the plasmin resistant crosslinked α chain regions of fibrin. The in vitro lysis of the pulmonary emboli by plasmin resulted in the production of soluble fragments called D dimer and E which are also associated with the lysis of plasma clots made in vitro. These similarities in the formation and lysis of in vitro and in vivo fibrins encourages the use of in vitro systems to help understand the initiation and progression of clinical thrombosis.

Binding of a new monoclonal antibody against N-terminal heptapeptide of fibrin α-chain to fibrin polymerization site ‘A’

1993 ◽  
Vol 4 (1) ◽  
pp. 79-86 ◽  
Author(s):  
C. E. Dempfle ◽  
M. Dollman ◽  
H. Lill ◽  
D. Puzzovio ◽  
A. Dessauer ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Fibrin Polymerization ◽  
Α Chain
Sign in / Sign up

Export Citation Format

Share Document