Two interesting cases of prolonged classical pathway convertase activity: C4NeF and a non-autoantibody serum factor

SummaryTrophoblasts from murine placenta synthesize thromboplastin in the absence of inducing agents and a functional complement system, nor is the rate or level of synthesis enhanced by inducers. A serum factor which is destroyed/removed by addition of oxalate and subsequent dialysis appears to enhance the ability of trophoblasts to synthesize thromboplastin.

Download Full-text

Prostacyclin Synthesis Is Stimulated by a Serum Factor Formed During Coagulation

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657316 ◽

1983 ◽

Vol 49 (01) ◽

pp. 058-060 ◽

Cited By ~ 12

Author(s):

J M Ritter ◽

M-A Ongari ◽

M A Orchard ◽

P J Lewis

Keyword(s):

Renal Failure ◽

Hydrolysis Product ◽

Healthy Controls ◽

Serum Factor ◽

Intrinsic Pathway ◽

Extrinsic Pathway ◽

Stimulatory Activity ◽

Plasma Factor ◽

Stimulating Factor ◽

Prostacyclin Synthesis

SummaryFresh aortic rings incubated in serum produce more 6-oxo-PGF1α, the stable hydrolysis product of prostacyclin, than in plasma or buffer. A method is described of recovering this stimulatory activity from a dialysate of serum, showing that the activity is due to a prostacyclin stimulating factor. This factor is formed during coagulation initiated by the intrinsic pathway but not by the extrinsic pathway or by thrombin. By contrast with a previously described plasma factor, the activity of the prostacy-clinstimulating factor in serum is not greater in serum from patients with renal failure than from healthy controls. The stimulating factor is antagonised by heparin, but differs in other ways from previously described platelet derived stimulating factor(s).

Download Full-text

INDUCTIVE AND INHIBITORY ACTIONS OF A LOW MOLECULAR WEIGHT SERUM FACTOR ON IN VITRO MATURATION OF OOCYTES OF THE MEDAKA

Biomedical Research ◽

10.2220/biomedres.8.313 ◽

1987 ◽

Vol 8 (5) ◽

pp. 313-322 ◽

Cited By ~ 3

Author(s):

TAKASHI IWAMATSU ◽

SUSUMU Y. TAKAHASHI ◽

NORIYOSHI SAKAI ◽

KAORI ASAI

Keyword(s):

Molecular Weight ◽

Low Molecular Weight ◽

Serum Factor

Download Full-text

The Crystal Structure of C2a, the Catalytic Fragment of Classical Pathway C3 and C5 Convertase of Human Complement

Journal of Molecular Biology ◽

10.1016/j.jmb.2006.12.039 ◽

2007 ◽

Vol 367 (1) ◽

pp. 224-233 ◽

Cited By ~ 26

Author(s):

Vengadesan Krishnan ◽

Yuanyuan Xu ◽

Kevin Macon ◽

John E. Volanakis ◽

Sthanam V.L. Narayana

Keyword(s):

Crystal Structure ◽

Classical Pathway ◽

Human Complement ◽

Catalytic Fragment

Download Full-text

Serum lectin with known structure activates complement through the classical pathway.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)47587-4 ◽

1987 ◽

Vol 262 (16) ◽

pp. 7451-7454 ◽

Cited By ~ 7

Author(s):

K Ikeda ◽

T Sannoh ◽

N Kawasaki ◽

T Kawasaki ◽

I Yamashina

Keyword(s):

Classical Pathway ◽

Serum Lectin

Download Full-text

Placental Complement Activation in Fetal and Neonatal Alloimmune Thrombocytopenia: An Observational Study

International Journal of Molecular Sciences ◽

10.3390/ijms22136763 ◽

2021 ◽

Vol 22 (13) ◽

pp. 6763

Author(s):

Thijs W. de Vos ◽

Dian Winkelhorst ◽

Hans J. Baelde ◽

Kyra L. Dijkstra ◽

Rianne D. M. van Bergen ◽

...

Keyword(s):

Complement Activation ◽

Histopathological Examination ◽

Hla Class I ◽

Unknown Etiology ◽

Low Grade ◽

Classical Pathway ◽

Newly Diagnosed ◽

Activation Markers ◽

Amsterdam Criteria ◽

Alloimmune Thrombocytopenia

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a disease that causes thrombocytopenia and a risk of bleeding in the (unborn) child that result from maternal alloantibodies directed against fetal, paternally inherited, human platelet antigens (HPA). It is hypothesized that these alloantibodies can also bind to the placenta, causing placental damage. This study aims to explore signs of antibody-mediated placental damage in FNAIT. We performed a retrospective study that included pregnant women, their newborns, and placentas. It comprised 23 FNAIT cases, of which nine were newly diagnosed (14 samples) and 14 were antenatally treated with intravenous immune globulins (IVIg) (21 samples), and 20 controls, of which 10 had anti-HLA-class I antibodies. Clinical information was collected from medical records. Placental samples were stained for complement activation markers (C1q, C4d, SC5b-9, and mannose-binding lectin) using immunohistochemistry. Histopathology was examined according to the Amsterdam criteria. A higher degree of C4d deposition was present in the newly diagnosed FNAIT cases (10/14 samples), as compared to the IVIg-treated FNAIT cases (2/21 samples, p = 0.002) and anti-HLA-negative controls (3/20 samples, p = 0.006). A histopathological examination showed delayed maturation in four (44%) placentas in the newly diagnosed FNAIT cases, five (36%) in the IVIg-treated FNAIT cases, and one in the controls (NS). C4d deposition at the syncytiotrophoblast was present in combination with low-grade villitis of unknown etiology in three newly diagnosed FNAIT cases that were born SGA. We conclude that a higher degree of classical pathway-induced complement activation is present in placentas from pregnancies with untreated FNAIT. This may affect placental function and fetal growth.

Download Full-text

Chronic complement dysregulation drives neuroinflammation after traumatic brain injury: a transcriptomic study

Acta Neuropathologica Communications ◽

10.1186/s40478-021-01226-2 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Amer Toutonji ◽

Mamatha Mandava ◽

Silvia Guglietta ◽

Stephen Tomlinson

Keyword(s):

Gene Expression ◽

Traumatic Brain Injury ◽

Brain Injury ◽

Complement System ◽

Classical Pathway ◽

Post Injury ◽

Complement Inhibition ◽

Time Points ◽

Complement Gene ◽

The Complement System

AbstractActivation of the complement system propagates neuroinflammation and brain damage early and chronically after traumatic brain injury (TBI). The complement system is complex and comprises more than 50 components, many of which remain to be characterized in the normal and injured brain. Moreover, complement therapeutic studies have focused on a limited number of histopathological outcomes, which while informative, do not assess the effect of complement inhibition on neuroprotection and inflammation in a comprehensive manner. Using high throughput gene expression technology (NanoString), we simultaneously analyzed complement gene expression profiles with other neuroinflammatory pathway genes at different time points after TBI. We additionally assessed the effects of complement inhibition on neuropathological processes. Analyses of neuroinflammatory genes were performed at days 3, 7, and 28 post injury in male C57BL/6 mice following a controlled cortical impact injury. We also characterized the expression of 59 complement genes at similar time points, and also at 1- and 2-years post injury. Overall, TBI upregulated the expression of markers of astrogliosis, immune cell activation, and cellular stress, and downregulated the expression of neuronal and synaptic markers from day 3 through 28 post injury. Moreover, TBI upregulated gene expression across most complement activation and effector pathways, with an early emphasis on classical pathway genes and with continued upregulation of C2, C3 and C4 expression 2 years post injury. Treatment using the targeted complement inhibitor, CR2-Crry, significantly ameliorated TBI-induced transcriptomic changes at all time points. Nevertheless, some immune and synaptic genes remained dysregulated with CR2-Crry treatment, suggesting adjuvant anti-inflammatory and neurotropic therapy may confer additional neuroprotection. In addition to characterizing complement gene expression in the normal and aging brain, our results demonstrate broad and chronic dysregulation of the complement system after TBI, and strengthen the view that the complement system is an attractive target for TBI therapy.

Download Full-text

Molecular and Functional Characterization of a ToxR-Regulated Lipoprotein from a Clinical Isolate of Aeromonas hydrophila

Infection and Immunity ◽

10.1128/iai.00402-06 ◽

2006 ◽

Vol 74 (7) ◽

pp. 3742-3755 ◽

Cited By ~ 22

Author(s):

Lakshmi Pillai ◽

Jian Sha ◽

Tatiana E. Erova ◽

Amin A. Fadl ◽

Bijay K. Khajanchi ◽

...

Keyword(s):

Virulence Factor ◽

Aeromonas Hydrophila ◽

Functional Characterization ◽

Affinity Column ◽

Serum Resistance ◽

Classical Pathway ◽

Dependent Manner ◽

T7 Promoter

ABSTRACT Human diseases caused by species of Aeromonas have been classified into two major groups: septicemia and gastroenteritis. In this study, we reported the molecular and functional characterization of a new virulence factor, ToxR-regulated lipoprotein, or TagA, from a diarrheal isolate, SSU, of Aeromonas hydrophila. The tagA gene of A. hydrophila exhibited 60% identity with that of a recently identified stcE gene from Escherichia coli O157:H7, which encoded a protein (StcE) that provided serum resistance to the bacterium and prevented erythrocyte lysis by controlling classical pathway of complement activation by cleaving the complement C1-esterase inhibitor (C1-INH). We purified A. hydrophila TagA as a histidine-tagged fusion protein (rTagA) from E. coli DE3 strain using a T7 promoter-based pET30 expression vector and nickel affinity column chromatography. rTagA cleaved C1-INH in a time-dependent manner. The tagA isogenic mutant of A. hydrophila, unlike its corresponding wild-type (WT) or the complemented strain, was unable to cleave C1-INH, which is required to potentiate the C1-INH-mediated lysis of host and bacterial cells. We indeed demonstrated colocalization of C1-INH and TagA on the bacterial surface by confocal fluorescence microscopy, which ultimately resulted in increased serum resistance of the WT bacterium. Likewise, we delineated the role of TagA in contributing to the enhanced ability of C1-INH to inhibit the classical complement-mediated lysis of erythrocytes. Importantly, we provided evidence that the tagA mutant was significantly less virulent in a mouse model of infection (60%) than the WT bacterium at two 50% lethal doses, which resulted in 100% mortality within 48 h. Taken together, our data provided new information on the role of TagA as a virulence factor in bacterial pathogenesis. This is the first report of TagA characterization from any species of Aeromonas.

Download Full-text