scholarly journals Assembly of contact-phase factors on the surface of the human neutrophil membrane

Blood ◽  
1994 ◽  
Vol 84 (2) ◽  
pp. 474-482 ◽  
Author(s):  
LM Henderson ◽  
CD Figueroa ◽  
W Muller-Esterl ◽  
KD Bhoola
Keyword(s):  
Binding Sites ◽  
Human Neutrophil ◽  
External Surface ◽  
Human Neutrophils ◽  
Phase System ◽  
Factor Xii ◽  
Tissue Kallikrein ◽  
The Novel ◽  
Contact Phase ◽  
Neutrophil Cell

Abstract H-kininogen (HK), a major factor involved in contact-phase activation, was recently immunolocalized on the external surface of human neutrophils. Experiments were, therefore, designed to consider the question of whether the complete assembly of contact factors occurs on the outer surface of the neutrophil membrane. By immunolocalization techniques, and using specific antibodies directed against the various contact factors, we now demonstrate that plasma prekallikrein (PK), factor XI (FXI), and factor XII (FXII) are present on the exterior face of the human neutrophil. Failure to localize HK, PK, or FXI by monoclonal antibodies directed to their reciprocal binding sites, and displacement of PK/FXI by peptide HK31, which mimics the relevant binding site(s) of HK, suggested that prekallikrein and FXI are anchored to the neutrophil membrane through attachment to the kininogen molecule. Probing of the kinin moiety by a specific antibody showed that kininogen molecules bound to the neutrophil cell membrane contain the kinin sequence, which can be released by plasma kallikrein or by tissue kallikrein. Our results led us to the novel conclusion that neutrophils provide a circulating platform for the components of the contact-phase system.

scholarly journals Assembly of contact-phase factors on the surface of the human neutrophil membrane

Blood ◽  
1994 ◽  
Vol 84 (2) ◽  
pp. 474-482 ◽  
Author(s):  
LM Henderson ◽  
CD Figueroa ◽  
W Muller-Esterl ◽  
KD Bhoola
Keyword(s):  
Binding Sites ◽  
Human Neutrophil ◽  
External Surface ◽  
Human Neutrophils ◽  
Phase System ◽  
Factor Xii ◽  
Tissue Kallikrein ◽  
The Novel ◽  
Contact Phase ◽  
Neutrophil Cell

H-kininogen (HK), a major factor involved in contact-phase activation, was recently immunolocalized on the external surface of human neutrophils. Experiments were, therefore, designed to consider the question of whether the complete assembly of contact factors occurs on the outer surface of the neutrophil membrane. By immunolocalization techniques, and using specific antibodies directed against the various contact factors, we now demonstrate that plasma prekallikrein (PK), factor XI (FXI), and factor XII (FXII) are present on the exterior face of the human neutrophil. Failure to localize HK, PK, or FXI by monoclonal antibodies directed to their reciprocal binding sites, and displacement of PK/FXI by peptide HK31, which mimics the relevant binding site(s) of HK, suggested that prekallikrein and FXI are anchored to the neutrophil membrane through attachment to the kininogen molecule. Probing of the kinin moiety by a specific antibody showed that kininogen molecules bound to the neutrophil cell membrane contain the kinin sequence, which can be released by plasma kallikrein or by tissue kallikrein. Our results led us to the novel conclusion that neutrophils provide a circulating platform for the components of the contact-phase system.

The assembly and activation of kinin-forming systems on the surface of human U-937 macrophage-like cells

2009 ◽  
Vol 390 (3) ◽  
Author(s):  
Anna Barbasz ◽  
Andrzej Kozik
Keyword(s):  
Cell Surface ◽  
Binding Sites ◽  
Plasma Proteins ◽  
Factor Xii ◽  
Tissue Kallikrein ◽  
Bulk Fluid ◽  
Cell Line Model ◽  
Inflammatory State ◽  
Generating System ◽  
Plasma Kinin

AbstractA complex of three plasma proteins, including the high molecular mass kininogen (HK), prekallikrein (PK), and factor XII (FXII), is known to assemble on cell surfaces to release bradykinin-related proinflammatory peptides (kinins). Only recently, the binding of HK to human macrophages was described in the U-937 cell line model. In the present study, the adsorption of the other components of plasma kinin-generating system to these cells was characterized. FXII was found to tightly bind to U-937 cells and was also shown to partially compete with HK for the same binding sites on the macrophage surface. The Mac-1 and gC1qR proteins were found to be receptors for FXII on the cell surface. PK indirectly docked to the macrophages via the cell-bound HK and FXII. Within the complex of these proteins assembled on the macrophage, PK could be activated by FXII/FXIIa or independently of this factor, and the active PK effectively released kinins from HK. The cell surface-bound HK could also be the substrate for tissue kallikrein approaching the cell from the bulk fluid. The kinins released at the surface are suggested to induce secondary responses in the macrophages, leading to further propagation of the inflammatory state.

scholarly journals Studies on the components of the contact phase system in patients with acute nonlymphoblastic leukemia

1997 ◽  
Vol 115 (4) ◽  
pp. 1490-1494
Author(s):  
Joyce Maria Annichino-Bizzacchi ◽  
Valder Roberval Arruda ◽  
Tania Fátima Gomes Machado ◽  
Andrea Maria Gallizoni ◽  
Cristina Cedran Ribeiro
Keyword(s):  
Prothrombin Time ◽  
Patient Group ◽  
Previous Treatment ◽  
Critical Value ◽  
Control Group ◽  
Phase System ◽  
Factor Xii ◽  
Factor V ◽  
Contact Phase ◽  
Acute Nonlymphoblastic Leukemia

The objective of the present study was to evaluate factors of the plasma kallikrein system in patients with acute nonlymphoblastic leukemia (ANLL), and compare the results to a normal control group. A prospective study was performed in the Tertiary Health Care Institution, Hemocentro, Campinas State University, Campinas, São Paulo, Brazil. Thirty-five patients, diagnosed as ANLL between 1988 and 1991, were considered for participation. Eleven patients were not elegible, according to the exclusion criteria: infection/ septicemia, previous treatment or blood transfusion. The study was performed with 24 ANLL patients, average age 34 years (16-69 years), 14 men and 10 women. Nineteen healthy volunteers, workers from the Hematology Center, average age 32 years (21-59 years), 11 men and 8 women, were the control group. Plasmatic prekallikrein, C1-inhibitor, alpha 2-macroglobulin, activated partial thromboplastin time, prothrombin time, factor XII, factor XI, factor V and prealbumin were measured. Plasmatic prekallikrein (p=0.02) and prealbumin (p=0.03) were significantly decreased, and prothrombin time increased (p=0.003) in the patient group when compared to the control. Significant correlation (r=0.49, critical value=0.43, p<0.05) between prekallikrein and prealbumin, and between prothrombin time and factor V (r=0.54, critical value=0.44, p<0.05) was demonstrated in the patient group. No correlation was found between parameters analysed and circulant blast count or leukemia subgroups. Statistical analysis was performed by theWilcoxon test. Correlation between the parameters was also verified. These results suggest activation of the contact system or impaired liver synthesis in patients with ANLL, and could contribute to disease complications.

Coagulation factor XII regulates inflammatory responses in human lungs

2017 ◽  
Vol 117 (10) ◽  
pp. 1896-1907 ◽  
Author(s):  
Christina Hesse ◽  
Katherina Sewald ◽  
Danny Jonigk ◽  
Gregor Warnecke ◽  
Hans-Gerd Fieguth ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Coagulation Factor ◽  
Phase System ◽  
Factor Xii ◽  
Contact Phase ◽  
Independent Manner ◽  
Human Lungs ◽  
Promising Therapeutic Approach ◽  
Tnf Α ◽  
Precision Cut Lung Slices

SummaryIncreased procoagulant activity in the alveolar compartment and uncontrolled inflammation are hallmarks of the acute respiratory distress syndrome (ARDS). Here, we investigated whether the contact phase system of coagulation is activated and may regulate inflammatory responses in human lungs. Components of the contact phase system were characterized in bronchoalveolar lavage fluids (BALF) from 54 ARDS patients and 43 controls, and their impact on cytokine/chemokine expression in human precision cut lung slices (PCLS) was assessed by a PCR array. Activation of the contact system, associated with high levels of coagulation factor XIIa (Hageman factor, FXIIa), plasma kallikrein and bradykinin, occurred rapidly in ARDS lungs after the onset of the disease and virtually normalized within one week from time of diagnosis. FXII levels in BALF were higher in ARDS nonsurvivors than survivors and were positively correlated with tumor necrosis factor (TNF)-α concentration. FXII induced the production and release of interleukin (IL)-8, IL-1β, IL-6, leukemia inhibitory factor (LIF), CXCL5 and TNF-α in human PCLS in a kallikrein-kinin-independent manner. In conclusion, accumulation of FXII in ARDS lungs may contribute to the release of pro-inflammatory mediators and is associated with clinical outcome. FXII inhibition may thus offer a novel and promising therapeutic approach to antagonize overwhelming inflammatory responses in ARDS lungs without interfering with vital haemostasis.Supplementary Material to this article is available online at www.thrombosis-online.com.

The Contact Phase of Blood Coagulation in Diabetes Mellitus and in Patients with Vasculopathy

1984 ◽  
Vol 52 (03) ◽  
pp. 221-223 ◽  
Author(s):  
M Christe ◽  
P Gattlen ◽  
J Fritschi ◽  
B Lämmle ◽  
W Berger ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Molecular Weight ◽  
Blood Coagulation ◽  
High Molecular Weight ◽  
Negative Correlation ◽  
Factor Xii ◽  
C1 Inhibitor ◽  
High Molecular Weight Kininogen ◽  
Contact Phase ◽  
Α2 Macroglobulin

SummaryThe contact phase has been studied in diabetics and patients with macroangiopathy. Factor XII and high molecular weight kininogen (HMWK) are normal. C1-inhibitor and also α2-macroglobulin are significantly elevated in diabetics with complications, for α1-macroglobulin especially in patients with nephropathy, 137.5% ± 36.0 (p <0.001). C1-inhibitor is also increased in vasculopathy without diabetes 113.2 ± 22.1 (p <0.01).Prekallikrein (PK) is increased in all patients’ groups (Table 2) as compared to normals. PK is particularly high (134% ± 32) in 5 diabetics without macroangiopathy but with sensomotor neuropathy. This difference is remarkable because of the older age of diabetics and the negative correlation of PK with age in normals.

The Flavonols Quercetin, Myricetin, Kaempferol, and Galangin Inhibit the Net Oxygen Consumption by Immune Complex- Stimulated Human and Rabbit Neutrophils

2014 ◽  
Vol 69 (7-8) ◽  
pp. 346-356 ◽  
Author(s):  
Andréa S. G. Figueiredo-Rinhel ◽  
Everton O. L. Santos ◽  
Luciana M. Kabeya ◽  
Ana Elisa C. S. Azzolini ◽  
Livia M. C. Simões-Ambrosio ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Immune Complex ◽  
Respiratory Burst ◽  
Human Neutrophil ◽  
Inflammatory Diseases ◽  
Cell Types ◽  
Oxygen Electrode ◽  
Experimental Models ◽  
Human Neutrophils ◽  
Experimental Conditions

Stimulated human neutrophils exhibit increased net oxygen consumption (NOC) due to the conversion of O2 into the superoxide anion by the NADPH oxidase enzymatic complex during the respiratory burst. In several inflammatory diseases, overproduction of these oxidants causes tissue damage. The present study aims to: (a) optimize the experimental conditions used to measure the NOC in serum-opsonized zymosan (OZ)-and insoluble immune complex (i-IC)-stimulated human and rabbit neutrophils; and (b) compare the effect of four flavonols (quercetin, myricetin, kaempferol, and galangin) on this activity. We used a Clark-type oxygen electrode to measure the NOC of stimulated neutrophils. Eliciting the neutrophil respiratory burst with OZ and i-IC yielded similar maximum O2 uptake levels within the same species, but the human neutrophil NOC was almost four times higher than the rabbit neutrophil NOC. The optimal experimental conditions established for both cell types were 4·106 neutrophils mL-1, 2 mg mL-1 OZ, and 240 µg mL-1 i-IC. Upon stimulation with OZ or i-IC, the tested flavonols reduced the human and rabbit neutrophil NOC in the same order of potency - quercetin and galangin were the most and the least potent, respectively. These compounds were around four times more effective in inhibiting the rabbit as compared to the human neutrophil NOC, respectively. The four flavonols were not toxic to human or rabbit neutrophils. The experimental conditions used are suitable for both the determination of human and rabbit neutrophil NOC and for the assessment of the modulatory effects of natural compounds on these activities. The relationship between the level of NOC and the inhibitory potency of the flavonols suggests that rabbit neutrophils can be useful experimental models to predict the effect of drugs on immune complexstimulated human neutrophils.

Targeted deletion of murine coagulation factor XII gene-a model for contact phase activation in vivo

2004 ◽  
Vol 92 (09) ◽  
pp. 503-508 ◽  
Author(s):  
Hans-Ulrich Pauer ◽  
Thomas Renné ◽  
Bernhard Hemmerlein ◽  
Tobias Legler ◽  
Saskia Fritzlar ◽  
...  
Keyword(s):  
Fetal Loss ◽  
Coagulation Factor ◽  
Coagulation Factors ◽  
Mendelian Inheritance ◽  
Biological Role ◽  
Factor Xii ◽  
Wild Type ◽  
Contact Phase ◽  
Health And Disease

SummaryTo analyze the biological role of factor XII (FXII, Hageman Factor) in vivo, we generated mice deficient for FXII using a gene targeting approach on two distinct genetic backgrounds, i.e. mixed C57Bl/6J X 129X1/SvJ and inbred 129X1/SvJ. Homozygous FXII knockout (FXII-/-) mice showed no FXII plasma activity and had a markedly prolonged activated partial thromboplastin time (aPTT). In contrast, coagulation factors XI, VIII, IX, X,VII,V, II and fibrinogen did not differ between FXII-/- mice and their wild-type littermates. Heterozygous matings segregated according to the Mendelian inheritance indicating that FXII deficiency does not increase fetal loss. Furthermore, matings of FXII-/- males and FXII-/females resulted in normal litter sizes demonstrating that total FXII deficiency in FXII-/females does not affect pregnancy outcome. Also, gross and histological anatomy of FXII-/mice was indistinguishable from that of their wild-type littermates on both genetic backgrounds. Thus it appears that deficiency of murine FXII does not cause thrombophilia or impaired fibrinolysis in vivo. These results indicate that FXII deficiency does not affect hemostasis in vivo and we anticipate that the FXII-/mice will be helpful to elucidate the biological role(s) of FXII in health and disease.

scholarly journals Studies on the electron-transfer mechanism of the human neutrophil NADPH oxidase

1989 ◽  
Vol 262 (2) ◽  
pp. 575-579 ◽  
Author(s):  
J A Ellis ◽  
A R Cross ◽  
O T G Jones
Keyword(s):  
Electron Transfer ◽  
Steady State ◽  
Nadph Oxidase ◽  
Cytochrome B ◽  
Human Neutrophil ◽  
Sodium Deoxycholate ◽  
Human Neutrophils ◽  
Electron Transfer Mechanism ◽  
State Reduction ◽  
O2 Production

A superoxide-generating NADPH oxidase was solubilized from phorbol 12-myristate 13-acetate-activated human neutrophils with a mixture of sodium deoxycholate (0.125%, w/v) and Lubrol-PX (0.125%, v/v). The solubilized preparation contained FAD (577 pmol/mg of protein) and cytochrome b-245 (479 pmol/mg of protein) and produced 11.61 mol of O2-./s per mol of cytochrome b (340 nmol of O2-./min per mg of protein). On addition of NADPH, the cytochrome b-245 was reduced by 7.9% and the FAD by 38% in the aerobic steady state; NADH addition caused little steady-state reduction of cytochrome b and FAD. In this preparation, and several others, the measured rate of O2-. production correlated with the turnover of cytochrome b calculated from the extent of cytochrome b-245 reduction under aerobic conditions. Addition of diphenyleneiodonium abolished the reduction of both the FAD and cytochrome b-245 components and inhibited O2-. production. The haem ligand imidazole inhibited O2-. generation and cytochrome b reduction while permitting FAD reduction. These results support the suggestion that the human neutrophil NADPH oxidase has the electron-transport sequence: NADPH-FAD-cytochrome b-245-O2.

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