scholarly journals Augmentation of macrophage complement receptor function in vitro. IV. The lymphokine that activates macrophage C3 receptors for phagocytosis binds to a fucose-bearing glycoprotein on the macrophage plasma membrane.

1984 ◽  
Vol 160 (4) ◽  
pp. 1206-1218 ◽  
Author(s):  
F M Griffin ◽  
P J Mullinax
Keyword(s):  
Plasma Membrane ◽  
Peritoneal Macrophages ◽  
Surface Glycoprotein ◽  
Complement C3 ◽  
Macrophage Receptors ◽  
C3 Receptors ◽  
Binding Lectin ◽  
Third Component Of Complement

Macrophage receptors for the third component of complement (C3) are normally immobilized and unable to diffuse within the cell's plasma membrane and, even though they promote avid particle binding, are unable to promote phagocytosis of C3-coated particles. We have previously identified a lymphokine that activates macrophage C3 receptors for phagocytosis and have found that it acts by freeing the receptors so that they can diffuse within the macrophage plasma membrane. It seemed likely to us that the initial lymphokine-macrophage interaction would occur at the macrophage surface, perhaps via a specific lymphokine receptor. Since the binding of many ligands to cells is mediated by cell surface glycoproteins, we examined the protein and sugar requirements for murine peritoneal macrophages to respond to the lymphokine. Macrophages treated with the neutral protease Dispase lost the ability to respond to the lymphokine, and inclusion of L-fucose in the incubation medium containing lymphokine and macrophages inhibited markedly the macrophages' response to the lymphokine, suggesting that the lymphokine exerts its effects by first binding to fucose residues on a glycoprotein receptor on the macrophage surface. Further evidence for the essential role of macrophage surface fucose was obtained by demonstrating that pretreatment of macrophages with either fucosidase or gorse lectin, a fucose-binding lectin, strikingly disabled the cells from responding to the lymphokine. All treatments that prevented lymphokine activation of macrophage C3 receptors for phagocytosis also prevented lymphokine-induced C3 receptor mobility. These results strongly suggest that the lymphokine binds to a fucose-bearing macrophage surface glycoprotein, perhaps a specific lymphokine receptor. They also strengthen our hypothesis that, for a receptor to be able to promote phagocytosis, it must be able to diffuse within the macrophage plasma membrane.

scholarly journals Studies on the mechanism of phagocytosis. I. Requirements for circumferential attachment of particle-bound ligands to specific receptors on the macrophage plasma membrane.

1975 ◽  
Vol 142 (5) ◽  
pp. 1263-1282 ◽  
Author(s):  
F M Griffin ◽  
J A Griffin ◽  
J E Leider ◽  
S C Silverstein
Keyword(s):  
Plasma Membrane ◽  
Sheep Erythrocyte ◽  
Peritoneal Macrophages ◽  
Membrane Receptors ◽  
Macrophage Receptors ◽  
Specific Receptors ◽  
Particle Ingestion ◽  
Plasma Membrane Receptors ◽  
Mouse Peritoneal Macrophages

These experiments were designed to evaluate the role of macrophage plasma membrane receptors for the third component of complement (C) and for the Fc portion of IgG in the ingestion phase of phagocytosis. Sheep erythrocyte (E) were coated with anti-E IgG [E(IgG)]; these E(IgG) were then attached to cultivated monolayers of mouse peritoneal macrophages under conditions which reversibly inhibit ingestion of E(IgG). The E(IgG)-macrophage complexes were further incubated under similar conditions with an antimacrophage IgG fraction which blocks Fc receptor-mediated ingestion but has no effect upon ingestion mediated by other phagocytic receptors. When these cultures were subsequently incubated under conditions optimal for particle ingestion, phagocytosis of the IgG-coated erythrocytes did not occur; the erythrocytes remained bound to the Fc receptors of the macrophage plasma membrane. To determine whether ligands must cover the entire surface of an attached particle to permit ingestion of that particle, C-coated E [E(IgM)C] were bound to the C receptors of thioglycollate-induced (activated) macrophages at 4 degrees C. E(IgM)C-macrophage complexes were then trypsinized at 4 degrees C, a procedure which resulted in cleavage of erythrocyte-bound C3b molecules to a form of C3 not recognized by the macrophage receptors for C3b. Under the conditions used, trypsin did not affect the attachment of E(IgM)C to the macrophage surface or the macrophage receptors for C3b. When these trypsin treated E(IgM)C-macrophage complexes were incubated at 37 degrees C, the bound E(IgM)C were not ingested; the erythrocytes remained attached to the macrophage plasma membrane via the macrophage's C receptors. These results indicate that attachment of a particle to specific receptors on the macrophage plasma membrane is not sufficient to trigger ingestion of that particle. Rather, ingestion requires the sequential, circumferential interaction of particle-bound ligands with specific plasma membrane receptors not involved in the initial attachment process.

The role of macrophage receptors in adhesion and uptake of Leishmania mexicana amastigotes

1995 ◽  
Vol 108 (12) ◽  
pp. 3715-3724 ◽  
Author(s):  
C. Peters ◽  
T. Aebischer ◽  
Y.D. Stierhof ◽  
M. Fuchs ◽  
P. Overath
Keyword(s):  
Protozoan Parasite ◽  
Mannose Receptor ◽  
Peritoneal Macrophages ◽  
Cos Cells ◽  
Macrophage Receptors ◽  
Type 3 ◽  
Kinetics Of

Amastigotes of the protozoan parasite Leishmania proliferate in phagolysosomes of mammalian macrophages. Propagation of the infection is considered to occur by host-cell rupture and uptake of released parasites by uninfected macrophages. In this study, the kinetics of binding of L mexicana mexicana amastigotes to COS cells and to COS cells transfected with three different macrophage receptors (FcRII-B2, receptor for the Fc-domain of immunoglobulins; CR3, complement type 3 receptor and the mannose receptor) is compared to the rate of adhesion to peritoneal macrophages. Amastigotes isolated from macrophages cultivated in vitro bind with slow, sigmoid kinetics to COS cells expressing either of the three receptors, or to peritoneal macrophages. In contrast, amastigotes isolated from mouse lesions bind with rapid, hyperbolic kinetics to COS cells expressing the Fc receptor or to peritoneal macrophages but with slow, sigmoid kinetics to COS cells expressing the CR3 or the mannose receptor. As shown by immunofluorescence experiments, lesion-derived amastigotes contain host-derived immunoglobulins (Ig) but no complement component 3 at their surface. It is concluded that amastigotes contain no intrinsic ligand at their surface, which enables high-affinity interactions with macrophages. Opsonization by specific Ig may be of relevance in vivo because firstly, in cryosections of mouse lesions extracellular amastigotes containing surface Ig can be detected and, secondly, B cell-deficient mice reconstituted with parasite-specific Ig show a modest increase in the rate of lesion development. In addition, it is shown that amastigotes are internalized by COS cells and grow in large parasitophorous vacuoles similar to those observed in macrophages.

scholarly journals Purinergic Modulation of Interleukin-1β Release from Microglial Cells Stimulated with Bacterial Endotoxin

1997 ◽  
Vol 185 (3) ◽  
pp. 579-582 ◽  
Author(s):  
Davide Ferrari ◽  
Paola Chiozzi ◽  
Simonetta Falzoni ◽  
Stefania Hanau ◽  
Francesco Di  Virgilio
Keyword(s):  
Plasma Membrane ◽  
P2x7 Receptor ◽  
Purinergic Receptor ◽  
Present Report ◽  
Physiological Role ◽  
Bacterial Endotoxin ◽  
Microglial Cells

Microglial cells express a peculiar plasma membrane receptor for extracellular ATP, named P2Z/P2X7 purinergic receptor, that triggers massive transmembrane ion fluxes and a reversible permeabilization of the plasma membrane to hydrophylic molecules of up to 900 dalton molecule weight and eventual cell death (Di Virgilio, F. 1995. Immunol. Today. 16:524–528). The physiological role of this newly cloned (Surprenant, A., F. Rassendren, E. Kawashima, R.A. North and G. Buell. 1996. Science (Wash. DC). 272:735–737) cytolytic receptor is unknown. In vitro and in vivo activation of the macrophage and microglial cell P2Z/P2X7 receptor by exogenous ATP causes a large and rapid release of mature IL-1β. In the present report we investigated the role of microglial P2Z/P2X7 receptor in IL-1β release triggered by LPS. Our data suggest that LPS-dependent IL-1β release involves activation of this purinergic receptor as it is inhibited by the selective P2Z/P2X7 blocker oxidized ATP and modulated by ATP-hydrolyzing enzymes such as apyrase or hexokinase. Furthermore, microglial cells release ATP when stimulated with LPS. LPS-dependent release of ATP is also observed in monocyte-derived human macrophages. It is suggested that bacterial endotoxin activates an autocrine/paracrine loop that drives ATP-dependent IL-1β secretion.

Effects of bafilomycin A1 on cytosolic pH of sheep alveolar and peritoneal macrophages: evaluation of the pH-regulatory role of plasma membrane V-ATPases.

1995 ◽  
Vol 198 (8) ◽  
pp. 1711-1715 ◽  
Author(s):  
T A Heming ◽  
D L Traber ◽  
F Hinder ◽  
A Bidani
Keyword(s):  
Plasma Membrane ◽  
Atpase Activity ◽  
Initial Rate ◽  
Cell Types ◽  
Peritoneal Macrophages ◽  
Bafilomycin A1 ◽  
Atpase Inhibitor ◽  
Cytosolic Ph ◽  
Phi Regulation

The role of plasma membrane V-ATPase activity in the regulation of cytosolic pH (pHi) was determined for resident alveolar and peritoneal macrophages (m theta) from sheep. Cytosolic pH was measured using 2',7'-biscarboxyethyl-5,6-carboxyfluorescein (BCECF). The baseline pHi of both cell types was sensitive to the specific V-ATPase inhibitor bafilomycin A1. Bafilomycin A1 caused a significant (approximately 0.2 pH units) and rapid (within seconds) decline in baseline pHi. Further, bafilomycin A1 slowed the initial rate of pHi recovery (dpHi/dt) from intracellular acid loads. Amiloride had no effects on baseline pHi, but reduced dpHi/dt (acid-loaded pHi nadir < 6.8) by approximately 35%. Recovery of pHi was abolished by co-treatment of m theta with bafilomycin A1 and amiloride. These data indicate that plasma membrane V-ATPase activity is a major determinant of pHi regulation in resident alveolar and peritoneal m theta from sheep. Sheep m theta also appear to possess a Na+/H+ exchanger. However, Na+/H+ exchange either is inactive or can be effectively masked by V-ATPase-mediated H+ extrusion at physiological pHi values.

scholarly journals A Critical Role of Activin A in Maturation of Mouse Peritoneal Macrophages in vitro and in vivo

2009 ◽  
Vol 6 (5) ◽  
pp. 387-392 ◽  
Author(s):  
Yinan Wang ◽  
Xueling Cui ◽  
Guixiang Tai ◽  
Jingyan Ge ◽  
Nan Li ◽  
...  
Keyword(s):  
Critical Role ◽  
Peritoneal Macrophages ◽  
Activin A ◽  
Mouse Peritoneal Macrophages

Multinucleated rat alveolar macrophages express functional receptors for calcitonin

1991 ◽  
Vol 261 (6) ◽  
pp. F1026-F1032 ◽  
Author(s):  
A. Vignery ◽  
M. J. Raymond ◽  
H. Y. Qian ◽  
F. Wang ◽  
S. A. Rosenzweig
Keyword(s):  
Plasma Membrane ◽  
Alveolar Macrophages ◽  
Giant Cells ◽  
Mononuclear Phagocytes ◽  
Inflammatory Reactions ◽  
Calcitonin Gene ◽  
Novel Model

The fusion of mononuclear phagocytes occurs spontaneously in vivo and leads to the differentiation of either multinucleated giant cells or osteoclasts in chronic inflammatory sites or in bone, respectively. Although osteoclasts are responsible for resorbing bone, the functional role of giant cells in chronic inflammatory reactions and tumors remains poorly understood. We recently reported that the plasma membrane of multinucleated macrophages is, like that of osteoclasts, enriched in Na-K-adenosinetriphosphatases (ATPases). We also observed that the localization of their Na-K-ATPases is restricted to the nonadherent domain of the plasma membrane of cells both in vivo and in vitro, thus imposing a functional polarity on their organization. By following this observation, we wished to investigate whether these cells also expressed, like osteoclasts, functional receptors for calcitonin (CT). To this end, alveolar macrophages were fused in vitro, and both their structural and functional association with CT was analyzed and compared with those of mononucleated peritoneal and alveolar macrophages. Evidence is presented that multinucleated alveolar macrophages express a high copy number of functional receptors for CT. Our results also indicate that alveolar macrophages, much like peritoneal, express functional receptors for calcitonin gene-related peptide. It is suggested that multinucleated rat alveolar macrophages offer a novel model system to study CT receptors and that calcitonin may control local immune reactions where giant cells differentiate.

scholarly journals Biosynthesis of pro-C3, a precursor of the third component of complement.

1977 ◽  
Vol 146 (3) ◽  
pp. 759-765 ◽  
Author(s):  
V Brade ◽  
R E Hall ◽  
H R Colten
Keyword(s):  
Disulfide Bonds ◽  
Polypeptide Chain ◽  
Peritoneal Macrophages ◽  
Tissue Cultures ◽  
The Third ◽  
Single Polypeptide Chain ◽  
Single Polypeptide ◽  
Polypeptide Chains ◽  
Third Component Of Complement

A precusor of the third component of complement, pro-C3, was detected in studies of cell-free synthesis and intracellularly in homogenates of liver tissue cultures. The molecular weight of pro-C3 was indistinguishable from that of intact native C3 secreted in vitro by liver or peritoneal macrophages, but its structure was different. Pro-C3 is a single polypeptide chain, whereas C3 secreted by cells in culture consists of two polypeptide chains (mol wt 120,000 and 76,000) linked by disulfide bonds.

Protein Disulfide Isomerase Regulates Sickle Erythrocyte Volume Via ET-1 Dependent Casein Kinase II Mechanism

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2114-2114
Author(s):  
Shirley D Valentin-Berrios ◽  
Jose R Romero ◽  
Alicia Rivera
Keyword(s):  
Plasma Membrane ◽  
Sickle Cell ◽  
Protein Disulfide Isomerase ◽  
Disulfide Isomerase ◽  
Sickle Erythrocyte ◽  
Cellular Dehydration ◽  
Sickle Erythrocytes ◽  
Protein Disulfide

Abstract Abstract 2114 Disordered K+ efflux and osmotically induced water loss leads to red blood cell (RBC) dehydration and plays a role in the pathophysiology of Sickle Cell Disease. We previously reported that activation of endothelin-1 (ET-1) receptors in sickle erythrocyte was partially responsible for dense sickle cell formation. However, the mechanism by which ET-1 regulates RBC volume remains unclear. Serine/threonine kinases have been shown to regulate K+ transport in RBC. Casein Kinase II (CK2), a serine/threonine kinase, phosphorylates acidic proteins, regulates calmodulin activity and cytoskeletal proteins and is present in RBC. CK2 activity is blocked by apigenin, emodin, heparin, and ornithine decarboxylase. Previous reports have shown a role for flavonoids such as apigenin as substrates for erythrocyte plasma membrane oxidoreductases. We recently observed a role for Protein Disulfide Isomerase (PDI) in regulating cellular hydration and K+ efflux in human RBC. PDI catalyzes disulfide interchange reactions in the plasma membrane, mediates redox modifications and is up-regulated under hypoxic conditions. However the relationship between CK2 and PDI in the setting of cellular hydration status is un-explored. Our results indicate that erythrocyte membrane CK2 activity increases when sickle cells are incubated with 500 nM ET-1 for 30 min (2.8 ± 0.1 to 4.9 ± 0.01 nmol/min/mL * 106 cell) an event that is blunted by pre-incubation with the ET-1 B receptor blocker, BQ788 (2.5 ± 0.1 nmol/min/mL * 106 cell, n=3, p<0.04) and 20 μM apigenin (2.7 ± 0.4 nmol/min/mL * 106 cell, n=3, p<0.04). We examined the role of CK2 activation on cellular dehydration. We incubated sickle erythrocytes for 3 hours in deoxygenation-oxygenation cycles in the presence or absence of 20μM apigenin or 2μM 4,5,6,7-tetrabromobenzotriazole (TBB), a specific CK2 inhibitor, and measured the changes in erythrocyte density by phthalate oil density analysis. We observed that inhibition of CK2 led to reduced deoxygenation-stimulated cellular dehydration in sickle erythrocytes by apigenin (D50= 1.106 to 1.100 g/mL) or TBB (D50 =1.097 g/mL). We then studied the role of CK2 inhibitors on PDI activity by Insulin Turbidity Assay and observed that apigenin and TBB led to significant reductions in PDI activity in vitro (64% and 42% respectively). We also studied the effects of the flavonoids: naringenin, naringin, apigenin and rutin on PDI activity and observed reductions in PDI activity that were greater with apigenin>rutin>TBB>naringin>naringenin (n=2, P<0.05). Furthermore, we observed that K+ flux via Gardos channel activation is correlated with PDI activity in vitro in sickle erythrocytes. Taken together our results implicate CK2 and PDI as intermediate regulators of ET-1 stimulated cellular volume systems in red blood cells. Supported by NIH R01-HL09632 to AR. Disclosures: No relevant conflicts of interest to declare.

Role of ESCRT component HD-PTP/PTPN23 in cancer

2017 ◽  
Vol 45 (3) ◽  
pp. 845-854 ◽  
Author(s):  
Marie-Claude Gingras ◽  
Jalal M. Kazan ◽  
Arnim Pause
Keyword(s):  
Plasma Membrane ◽  
Cancer Susceptibility ◽  
Tumour Suppressor ◽  
Tumour Suppressor Genes ◽  
Surface Receptors ◽  
Endosomal Sorting ◽  
Bona Fide

Sustained cellular signalling originated from the receptors located at the plasma membrane is widely associated with cancer susceptibility. Endosomal sorting and degradation of the cell surface receptors is therefore crucial to preventing chronic downstream signalling and tumorigenesis. Since the Endosomal Sorting Complexes Required for Transport (ESCRT) controls these processes, ESCRT components were proposed to act as tumour suppressor genes. However, the bona fide role of ESCRT components in tumorigenesis has not been clearly demonstrated. The ESCRT member HD-PTP/PTPN23 was recently identified as a novel haplo-insufficient tumour suppressor in vitro and in vivo, in mice and humans. In this mini-review, we outline the role of the ESCRT components in cancer and summarize the functions of HD-PTP/PTPN23 in tumorigenesis.

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