scholarly journals Effect of C3b inactivator on monocyte-bound C3-coated human erythrocytes

Blood ◽  
1978 ◽  
Vol 52 (5) ◽  
pp. 896-904 ◽  
Author(s):  
AD Schreiber ◽  
PB McDermott
Keyword(s):  
Attachment Site ◽  
Human Erythrocytes ◽  
Red Cells ◽  
Dependent Manner ◽  
Phagocytic Cells ◽  
Complement Components ◽  
Serum Factors ◽  
Igm Antibody ◽  
Erythrocyte Surface ◽  
Membrane Bound

Abstract As a model of IgM-induced hemolytic anemia in man, human erythrocytes were sensitized with IgM antibody and coated with complement components, including C3 and C4, using human serum as a source of complement. These coated red cells were then interacted with monolayers of human mononuclear phagocytic cells (monocytes). Complement-coated red cells so bound could be displaced from their monocyte attachment site in a dose- and time-dependent manner by serum factors, including C3b inactivator (C3bINA). These factors were more efficient in inactivating red cell-bound complement components prior to interaction of the coated cells with monocytes. With large amounts of complement per erythrocyte, measured as membrane-bound C3, the ability of the serum inactivating factor(s) to remove the complement-coated red cells from the monocyte surface was compromised and persistently bound red cells were progressively phagocytosed. These studies implicate C3bINA in the displacement of complement-coated erythrocytes, formed from the interaction of IgM antibody and serum complement, from the hepatic macrophage in IgM-induced immune hemolysis. They suggest that both the concentration of complement components, especially on the erythrocyte surface, and the level of C3bINA and perhaps other inactivators may be important features regulating hemolysis in this disorder.

scholarly journals Effect of C3b inactivator on monocyte-bound C3-coated human erythrocytes

Blood ◽  
1978 ◽  
Vol 52 (5) ◽  
pp. 896-904
Author(s):  
AD Schreiber ◽  
PB McDermott
Keyword(s):  
Attachment Site ◽  
Human Erythrocytes ◽  
Red Cells ◽  
Dependent Manner ◽  
Phagocytic Cells ◽  
Complement Components ◽  
Serum Factors ◽  
Igm Antibody ◽  
Erythrocyte Surface ◽  
Membrane Bound

As a model of IgM-induced hemolytic anemia in man, human erythrocytes were sensitized with IgM antibody and coated with complement components, including C3 and C4, using human serum as a source of complement. These coated red cells were then interacted with monolayers of human mononuclear phagocytic cells (monocytes). Complement-coated red cells so bound could be displaced from their monocyte attachment site in a dose- and time-dependent manner by serum factors, including C3b inactivator (C3bINA). These factors were more efficient in inactivating red cell-bound complement components prior to interaction of the coated cells with monocytes. With large amounts of complement per erythrocyte, measured as membrane-bound C3, the ability of the serum inactivating factor(s) to remove the complement-coated red cells from the monocyte surface was compromised and persistently bound red cells were progressively phagocytosed. These studies implicate C3bINA in the displacement of complement-coated erythrocytes, formed from the interaction of IgM antibody and serum complement, from the hepatic macrophage in IgM-induced immune hemolysis. They suggest that both the concentration of complement components, especially on the erythrocyte surface, and the level of C3bINA and perhaps other inactivators may be important features regulating hemolysis in this disorder.

The cytoprotective effects of bilirubin and biliverdin on rat hepatocytes and human erythrocytes and the impact of albumin

1991 ◽  
Vol 69 (12) ◽  
pp. 828-834 ◽  
Author(s):  
Tai-Wing Wu ◽  
Doug Carey ◽  
Jun Wu ◽  
Hiroshi Sugiyama
Keyword(s):  
Rat Hepatocytes ◽  
Human Erythrocytes ◽  
Red Cells ◽  
Peroxyl Radicals ◽  
Blood Levels ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Hepatocyte Necrosis ◽  
The Impact ◽  
First Time

The hypothesis that unconjugated bilirubin and biliverdin are cytoprotective antioxidants has been examined for the first time in systems containing cells. In primary rat hepatocytes exposed to xanthine oxidase and hypoxanthine, bilirubin (0–60 μM) failed to prolong cell survival. In contrast, biliverdin (20–100 μM) markedly delayed hepatocyte necrosis in a concentration-dependent manner. When 0.3 mM of albumin was present, bilirubin (0–50 μM) became protective of hepatocytes, while biliverdin was less dramatically enhanced in its cytoprotective effect. In human erythrocytes exposed to peroxyl radicals, bilirubin and biliverdin inhibited 50% cell lysis at lower concentrations than Trolox and ascorbate, respectively. Albumin alone appeared less cytoprotective in red cells than in hepatocytes, but its presence enhanced the effects of both pigments on erythrocytes. Of probable physiologic relevance, bilirubin with albumin present or biliverdin alone protected hepatocytes substantially (and to a lesser extent red cells) at the normal blood levels of bilirubin (3.4–26 μM). Moreover, the fact that the pigments are cytoprotective at higher bilirubin levels (e.g., 50–100 μM) tempts the speculation that they may be circulating cytoprotectors of overlooked importance in jaundice.Key words: cytoprotection, biliverdin, bilirubin, albumin.

Effect of Lectins and Chemical Modification on the Hemagglutinin Activity of Human Plasma Fibronectin

1981 ◽  
Vol 36 (9-10) ◽  
pp. 863-868 ◽  
Author(s):  
Matti Vuento ◽  
Eija Salonen
Keyword(s):  
Chemical Modification ◽  
Human Plasma ◽  
Present Report ◽  
Red Cells ◽  
Carboxyl Groups ◽  
Plasma Fibronectin ◽  
Cell Surfaces ◽  
Serum Factors ◽  
Low Concentrations ◽  
Erythrocyte Surface

Abstract Purified hum an plasm a fibronectin has been shown to agglutinate protease-treated red cells [Vuento, Hoppe-Seyler's Z. Physiol. Chem. 360, 1327-1333, (1979)]. The present report shows that the activity is inhibited by low concentrations of lectins and by macrom olecular serum factors. Chemical m odification of carboxyl groups of fibronectin strongly inhibited the activity, but modification of am ino groups or guanidinium groups had little effect on the activity. The results suggest that fibronectin receptors on erythrocyte surface are carbohydrate-containing molecules. Humoral m acrom olecular factors may control the interaction of fibronectin with cell surfaces. Chemical m odification studies indicate that the parts of the fibronectin molecule responsible for the hem agglutinin activity are different from those mediating the binding of fibronectin to collagen.

scholarly journals MOTION PICTURE STUDIES ON DEGRANULATION OF HORSE EOSINOPHILS DURING PHAGOCYTOSIS

1963 ◽  
Vol 118 (2) ◽  
pp. 287-294 ◽  
Author(s):  
Gordon T. Archer ◽  
James G. Hirsch
Keyword(s):  
Yeast Cell ◽  
Cell Walls ◽  
Inhibitory Effect ◽  
Red Cells ◽  
Red Cell ◽  
Phagocytic Cells ◽  
Serum Factors ◽  
Antigen Antibody ◽  
Glass Surfaces

Horse eosinophil function has been studied in vitro by means of phase contrast cinemicrophotography. Locomotion of horse eosinophils was inhibited by serum factors reacting with glass surfaces. Under appropriate conditions which eliminated this inhibitory effect, eosinophils moved about and ingested some particles as rapidly as did neutrophils. Eosinophils were attracted to and readily engulfed such diverse materials as yeast cell walls, foreign erythrocytes, and antigen-antibody precipitates. Specific antibody was required for phagocytosis of red cells, and greatly accelerated the uptake of yeast cell walls. Horse eosinophil granules situated adjacent to material being engulfed disrupted with discharge of granule contents into or alongside the phagocytic vacuole. Granule disruption resulted in a clear zone and deposition of amorphous, phase-dense material. A heat-labile serum factor was required for degranulation of eosinophils ingesting foreign red cells, but not for degranulation during engulfment of yeast cell walls or antigen-antibody precipitates. Horse eosinophils were incapable under these conditions of engulfing an entire human red cell. The eosinophil commonly put out a large pseudopod to surround about half the red cell, and then appeared to constrict this pseudopod distally to cut the erythrocyte in half. It is concluded that eosinophils are phagocytic cells, resembling neutrophils in many of their properties. Any specific functions of eosinophils, distinguishing them from other phagocytes, remain to be discovered.

scholarly journals CSF1R Is Associated with Poor Overall Survival in AML and Mediates Supportive Interactions Between AML and Stromal Cells in the AML Microenvironment

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2666-2666 ◽  
Author(s):  
Ayesha Rashid ◽  
Irakli Dzneladze ◽  
Ruijuan He ◽  
John F Woolley ◽  
Michael D Jain ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stromal Cells ◽  
Myeloid Cell ◽  
Leukemic Cells ◽  
Stem Cell Markers ◽  
Dependent Manner ◽  
Phagocytic Cells ◽  
Poor Overall Survival ◽  
Membrane Bound

Abstract Bone marrow (BM) stromal cells produce factors important for the growth and maintenance of normal hematopoietic, as well as leukemic cells. Interactions between hematopoietic and stromal cells as mediated by classic ligand-receptor, cytokine and metabolic elements help to create a supportive microenvironmental niche. Colony stimulating factor 1 (CSF1) is a cytokine produced by BM stromal cells. CSF1 exists as both secreted and membrane-bound isoforms, with the latter being predominant in the BM. CSF1 acts on the CSF1 receptor (CSF1R), which is expressed on phagocytic cells to induce their growth and differentiation into monocytes, macrophages and dendritic cells. Acute myeloid leukemia (AML) arises from mutations that lead to a block in differentiation of myeloid cell precursors (myeloblast or blast cells), the accumulation of which interferes with normal hematopoiesis. In this study, we examined the role of the CSF1-CSF1R interaction in AML as related to patient outcome and its influence on AML-stromal cell interactions. Analysis of cell surface protein levels of CSF1R by flow cytometry revealed that a subset of AML patient samples express high levels of CSF1R (CSF1Rhigh). Clinically, we found that CSF1Rhigh patients have shorter overall survival compared to patients with low CSF1R expression. To examine the CSF1-CSF1R interaction experimentally, CSF1Rhigh AML cells (patient samples and cell lines) were grown in in-vitro co-cultures with murine MS5 stromal cells engineered to overexpress the membrane-bound form of human CSF1 (MS5-hCSF1). We found that MS5-hCSF1 stromal cells display an increased growth rate, altered cytokine profile and signaling changes (namely mTOR pathway activation) compared to cells that do not express CSF1. In co-culture assays, we found that MS5-hCSF1 stromal cells enhanced the long-term growth (2 weeks) and survival of CSF1Rhigh AML cells by several fold. This growth advantage was not observed for CSF1RlowAML cells. Pre-culture of AML cells with MS5-hCSF1 stromal cells for 72 hours led to increased colony numbers in colony forming unit (CFU) assays compared to pre-culture on non-CSF1-expressing stroma. This suggests that exposure to CSF1 may enhance the clonogenic potential of AML cells. Co-culture of AML cells with MS5-hCSF1 stromal cells led to increased surface expression of the stem cell markers CD34 and CD117 (c-kit), suggestive of an immature, progenitor-like AML phenotype driven by CSF1. Furthermore, co-culture of AML and MS5-hCSF1 stromal cells led to distinct changes in the cytokine profiles of both AML and stromal cells, with increased levels of IL-8, IL-10 and IL-1 RA and RANTES in AML cells, and increased levels of IL-3, IL-6 and VEGF in stromal cells. Taken together, these results suggest that the CSF1-CSF1R interaction may be important in promoting a pro-leukemic phenotype. In particular, stromal support of AML is enhanced in a CSF1-dependent manner, with effects on AML growth, differentiation and production of signaling molecules. These effects in turn, have implications for modulating stromal cells themselves. Studying and understanding the complex interplays between AML and stromal cells as driven by the CSF1-CSF1R interaction may aid in the development of therapeutic approaches to target AML and its niche environment. Disclosures Jain: Roche Canada: Research Funding.

Hemoglobin Enhances the Binding of Bacterial Endotoxin to Human Endothelial Cells

1996 ◽  
Vol 76 (02) ◽  
pp. 258-262 ◽  
Author(s):  
Robert I Roth
Keyword(s):  
Endothelial Cells ◽  
Binding Protein ◽  
Bacterial Endotoxin ◽  
Dependent Manner ◽  
Serum Free Medium ◽  
Free Medium ◽  
Human Endothelial Cells ◽  
Serum Factors ◽  
Serum Free ◽  
Lps Binding

SummaryHuman endothelial cells, when incubated with bacterial endotoxin (lipopolysaccharide, LPS), modify their surface in association with prominent production of procoagulant tissue factor (TF) activity. This deleterious biological effect of LPS has been shown previously to be enhanced approximately 10-fold by the presence of hemoglobin (Hb), a recently recognized LPS binding protein that causes disaggregation of LPS and increases the biological activity of LPS in a number of in vitro assays. The present study was performed to test the hypothesis that Hb enhances the LPS-induced procoagulant activity of human umbilical vein endothelial cells (HUVEC) by increasing LPS binding to the cells. The binding of 3H-LPS to HUVEC was determined in the absence or presence of Hb or two other known LPS-binding proteins, human serum albumin (HSA) and IgG. LPS binding was substantially increased in the presence of Hb, in a Hb concentration-dependent manner, but was not increased by HSA or IgG. Hb enhancement of LPS binding was observed in serum-free medium, indicating that there was no additional requirement for any of the serum factors known to participate in the interaction of LPS with cells (e.g., lipopolysaccharide (LPS)-binding protein (LBP) and soluble CD14 (sCD14)). Hb enhancement of LPS binding also was observed in the more physiologic condition of 100% plasma. LPS-induced TF activity was stimulated by Hb, but not by HSA or IgG. In serum-free medium, TF activity was not stimulated under any of the conditions tested. Ultrafiltration of LPS was dramatically increased after incubation with Hb but not with HSA or IgG, suggesting that LPS disaggregation by Hb was responsible for the enhanced binding of LPS to HUVEC and the subsequent stimulation of TF activity.

scholarly journals Isolation and characterization of a membrane protein from rat erythrocytes which inhibits lysis by the membrane attack complex of rat complement

1992 ◽  
Vol 284 (1) ◽  
pp. 169-176 ◽  
Author(s):  
T R Hughes ◽  
S J Piddlesden ◽  
J D Williams ◽  
R A Harrison ◽  
B P Morgan
Keyword(s):  
Affinity Purification ◽  
Membrane Attack Complex ◽  
Erythrocyte Membranes ◽  
Dependent Manner ◽  
Inhibitory Protein ◽  
Rat Erythrocytes ◽  
Butanol Extract ◽  
Isolation And Characterization ◽  
Membrane Bound

The membrane attack complex (MAC) of complement in humans is regulated by several membrane-bound proteins; however, no such proteins have so far been described in other species. Here we report the isolation and characterization of a rat erythrocyte membrane glycoprotein of molecular mass 21 kDa which inserts into cell membranes and is a potent inhibitor of the rat MAC. This protein, here called rat inhibitory protein (RIP), was first partially purified by column chromatography from a butanol extract of rat erythrocyte membranes. Monoclonal antibodies (Mabs) were raised against RIP and used for its affinity purification. Affinity-purified RIP was shown to inhibit in a dose-dependent manner the cobra venom factor (CVF)-mediated ‘reactive’ lysis of guinea pig erythrocytes by rat complement. Conversely, the anti-RIP MAbs 6D1 and TH9 were shown to markedly enhance the CVF-mediated lysis of rat erythrocytes by rat complement. RIP acted late in the assembly of the MAC (at or after the C5b-8 stage) and was releasable from the membranes of rat erythrocytes by phosphatidylinositol-specific phospholipase C. These features, together with its size, deglycosylation pattern and N-terminal amino acid sequence, lead us to conclude that RIP is the rat homologue of the human MAC-inhibitory protein CD59 antigen.

Topics in Chronic Granulomatous Disease

PEDIATRICS ◽  
1991 ◽  
Vol 88 (1) ◽  
pp. 183-185
Author(s):  
SHIGENOBU UMEKI
Keyword(s):  
Nadph Oxidase ◽  
Chronic Granulomatous Disease ◽  
Host Defense ◽  
Superoxide Anion ◽  
Fungal Infections ◽  
Regulatory Elements ◽  
Granulomatous Disease ◽  
Phagocytic Cells ◽  
Oxidase System ◽  
Membrane Bound

To the Editor.— Such phagocytic cells as neutrophils and macrophages are crucial elements in the host defense against bacterial [See table in the PDF file] and fungal infections. Microbicidal activity depends to a large extent on NADPH oxidase system, which can be activated by stimuli (bacteria, fungi) and which generates the superoxide anion and other highly reactive forms of reduced oxygen.1,2 The neutrophil NADPH oxidase system is composed functionally of membrane-bound catalytic components (which consist of at least two constituents, the low potential cytochrome b5583-5 and flavoprotein5) and soluble cytosolic components6,7 which participate as either catalytic or regulatory elements.

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