scholarly journals C3 Opsonization of Anthrax Bacterium and Peptidoglycan Supports Recognition and Activation of Neutrophils

2020 ◽  
Vol 8 (7) ◽  
pp. 1039
Author(s):  
Narcis I. Popescu ◽  
Ravi S. Keshari ◽  
Jackie Cochran ◽  
K. Mark Coggeshall ◽  
Florea Lupu
Keyword(s):  
Complement C3 ◽  
Immune Recognition ◽  
Complement Receptors ◽  
Molecular Pattern ◽  
Lower Extent ◽  
Independent Mechanism ◽  
Neutrophil Degranulation ◽  
Particle Ingestion ◽  
C5a Anaphylatoxin

Neutrophils are the most abundant innate cell population and a key immune player against invading pathogens. Neutrophils can kill both bacterium and spores of Bacillus anthracis, the causative anthrax pathogen. Unlike interactions with professional phagocytes, the molecular recognition of anthrax by neutrophils is largely unknown. In this study, we investigated the role of complement C3 deposition on anthrax particles for neutrophil recognition of bacterium and/or its cell wall peptidoglycan, an abundant pathogen-associated molecular pattern that supports anthrax sepsis. C3 opsonization and recognition by complement receptors accounted for 70–80% of the affinity interactions between neutrophils and anthrax particles at subphysiologic temperatures. In contrast, C3 supported up to 50% of the anthrax particle ingestion under thermophysiologic conditions. Opsonin-dependent low affinity interactions and, to a lower extent, opsonin-independent mechanisms, provide alternative entry routes. Similarly, C3 supported 58% of peptidoglycan-induced degranulation and, to a lower extent, 23% of bacterium-induced degranulation. Interestingly, an opsonin independent mechanism mediated by complement C5, likely through C5a anaphylatoxin, primes azurophilic granules in response to anthrax particles. Overall, we show that C3 deposition supports anthrax recognition by neutrophils but is dispensable for pathogen ingestion and neutrophil degranulation, highlighting immune recognition redundancies that minimize the risk of pathogen evasion.

scholarly journals The role of membrane receptors for C3b and C3d in phagocytosis.

1977 ◽  
Vol 145 (2) ◽  
pp. 357-371 ◽  
Author(s):  
A G Ehlenberger ◽  
V Nussenzweig
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Polymorphonuclear Leukocytes ◽  
Membrane Receptors ◽  
The Other ◽  
Necessary Condition ◽  
Complement Receptors ◽  
Human Monocytes ◽  
Particle Ingestion

In this paper we re-examine the roles of particle-bound IgG and C3 in phagocytosis of sheep erythrocytes (E) by monolayers of purified human monocytes and polymorphonuclear leukocytes (PMN). We conclude that two fragments of the C3 molecule, that is, C3b and C3d, can function as opsonins if the phagocyte has the appropriate membrane receptors. Monocytes, that bind both C3b and C3d, respond to both as opsonins. PMN, which do not bind C3d, respond only to particles opsonized with C3b. C3 and IgG have separate roles in phagocytosis. IgG, through its Fc fragment, directly stimulates particle ingestion, but is relatively inefficient at inducing particle binding. On the other hand, C3 primarily mediates the binding of the particle via complement receptors. A marked synergy exists between C3 and IgG in inducing phagocytosis. Thus, opsonization of the particle with C3 can be a necessary condition for particle ingestion, although by itself C3 does not trigger phagocytosis. The opsonic effect of C3 can be mimicked by a variety of nonimmunologic agents which enhance binding of the particle to the phagocyte without directly stimulating ingestion. The contact-inducing agents used include centrifugation of particle and phagocyte, high molecular weight dextran, protamine, and treatment of E with neuraminidase. These results suggest that the role of C3 in opsonization is mainly or exclusively one of establishing contact between particle and phagocyte.

The Role of High Mobility Group Box 1 (HMGB1) in Neurodegeneration: A Systematic Review

2022 ◽  
Vol 20 ◽  
Author(s):  
Fathimath Zaha Ikram ◽  
Alina Arulsamy ◽  
Thaarvena Retinasamy ◽  
Mohd. Farooq Shaikh
Keyword(s):  
Systematic Review ◽  
Tissue Injury ◽  
High Mobility ◽  
High Mobility Group ◽  
Hmgb1 Protein ◽  
Toll Like Receptor 4 ◽  
Neuroinflammatory Response ◽  
Molecular Pattern ◽  
Glycation End Products

Background: High mobility group box 1 (HMGB1) protein is a damage-associated molecular pattern (DAMP) molecule that plays an important role in the repair and regeneration of tissue injury. It also acts as a pro-inflammatory cytokine through the activation of toll-like receptor 4 (TLR4) and receptor for advanced glycation end products (RAGE), to elicit the neuroinflammatory response. HMGB1 may aggravate several cellular responses which may lead to pathological inflammation and cellular death. Thus, there have been a considerable amount of research into the pathological role of HMGB1 in diseases. However, whether the mechanism of action of HMGB1 is similar in all neurodegenerative disease pathology remains to be determined. Objective: Therefore, this systematic review aimed to critically evaluate and elucidate the role of HMGB1 in the pathology of neurodegeneration based on the available literature. Methods: A comprehensive literature search was performed on four databases; EMBASE, PubMed, Scopus, and CINAHL Plus. Results: A total of 85 articles were selected for critical appraisal, after subjecting to the inclusion and exclusion criteria in this study. The selected articles revealed that HMGB1 levels were found elevated in most neurodegeneration except in Huntington’s disease and Spinocerebellar ataxia, where the levels were found decreased. This review also showcased that HMGB1 may act on distinctive pathways to elicit its pathological response leading to the various neurodegeneration processes/diseases. Conclusion: While there have been promising findings in HMGB1 intervention research, further studies may still be required before any HMGB1 intervention may be recommended as a therapeutic target for neurodegenerative diseases.

Immune complex binding Streptococcus pyogenes type M12/emm12 in experimental glomerulonephritis

2013 ◽  
Vol 62 (9) ◽  
pp. 1272-1280 ◽  
Author(s):  
Larissa Burova ◽  
Peter Pigarevsky ◽  
Nadezhda Duplik ◽  
Vlada Snegova ◽  
Alexander Suvorov ◽  
...  
Keyword(s):  
Rabbit Model ◽  
Complement C3 ◽  
Poststreptococcal Glomerulonephritis ◽  
Tnf Α ◽  
Rabbit Igg ◽  
Renal Changes ◽  
Group A ◽  
Study Type ◽  
Binding Component

In a rabbit model, we have previously reported evidence for a pathogenic role of streptococcal IgG Fc-binding proteins (IgGFcBP) in poststreptococcal glomerulonephritis (PSGN). These proteins, of the M protein family, were shown to trigger anti-IgG production and enhance renal deposition of IgG and/or immune complexes (ICs), with resulting activation of complement and cytokine cascades. In the present study, type M12/emm12, group A streptococci (GAS) were found often to bind artificial ICs, viz. peroxidase–anti-peroxidase rabbit IgG (PAP) or tetanus toxoid–anti-tetanus human IgG (TAT), rather than monomeric IgG. Animals injected with each of four IC binding clinical isolates (from patients with scarlet fever or PSGN) showed pronounced inflammatory and degenerative glomerular changes, morphologically similar to human PSGN, with membrane thickening and IgG and complement C3 deposition, as well as secretion of IL-6 and TNF-α by mesangial and endothelial cells. In contrast, non-binding strains (two from asymptomatic carriers and one from a PSGN case) failed to trigger any renal changes. Only the IC binding strains induced elevated titres of anti-IgG. Though the streptococcal binding component(s) has not been demonstrated, the selective binding of ICs by type M12/emm12 strains appears important for the well-known, marked nephritogenic potential of this GAS type.

scholarly journals Effect of time and vascular pressure on permeability and cyclic nucleotides in ischemic lungs

2000 ◽  
Vol 279 (5) ◽  
pp. H2077-H2084 ◽  
Author(s):  
David B. Pearse ◽  
Patrice M. Becker
Keyword(s):  
Nitric Oxide ◽  
High Pressure ◽  
Reflection Coefficient ◽  
Cyclic Nucleotides ◽  
Fluid Flux ◽  
No Donor ◽  
Independent Mechanism ◽  
Dependent Mechanism ◽  
Intravascular Pressure

We previously found that increased intravascular pressure decreased ischemic lung injury by a nitric oxide (NO)-dependent mechanism (Becker PM, Buchanan W, and Sylvester JT. J Appl Physiol 84: 803–808, 1998). To determine the role of cyclic nucleotides in this response, we measured the reflection coefficient for albumin (ςalb), fluid flux ( J˙), cGMP, and cAMP in ferret lungs subjected to either 45 min (“short”; n = 7) or 180 min (“long”) of ventilated ischemia. Long ischemic lungs had “low” (1–2 mmHg, n = 8) or “high” (7–8 mmHg, n = 6) vascular pressure. Other long low lungs were treated with the NO donor ( Z)-1-[ N-(3-ammoniopropyl)- N-( n-propyl)amino]diazen-1-ium-1,2-diolate (PAPA-NONOate; 5 × 10−4 M, n = 6) or 8-bromo-cGMP (5 × 10−4 M, n = 6). Compared with short ischemia, long low ischemia decreased ςalb (0.23 ± 0.04 vs. 0.73 ± 0.08; P < 0.05) and increased J˙ (1.93 ± 0.26 vs. 0.58 ± 0.22 ml · min−1 · 100 g−1; P < 0.05). High pressure prevented these changes. Lung cGMP decreased by 66% in long compared with short ischemia. Lung cAMP did not change. PAPA-NONOate and 8-bromo-cGMP increased lung cGMP, but only 8-bromo-cGMP decreased permeability. These results suggest that ischemic vascular injury was, in part, mediated by a decrease in cGMP. Increased vascular pressure prevented injury by a cGMP-independent mechanism that could not be mimicked by administration of exogenous NO.

scholarly journals Generation of Novel Human Red Blood Cell-Bearing Humanized Mouse Models Based on C3-Deficient NOG Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Takuya Yamaguchi ◽  
Ikumi Katano ◽  
Iyo Otsuka ◽  
Ryoji Ito ◽  
Misa Mochizuki ◽  
...  
Keyword(s):  
Mouse Models ◽  
Complement C3 ◽  
Humanized Mouse ◽  
Hematopoietic Stem ◽  
Gm Csf ◽  
Human Red Blood Cells ◽  
Mouse Macrophages ◽  
C3 Gene ◽  
Humanized Mouse Models

Despite recent advances in immunodeficient mouse models bearing human red blood cells (hRBCs), the elimination of circulating hRBCs by residual innate immune systems remains a significant challenge. In this study, we evaluated the role of mouse complement C3 in the elimination of circulating hRBCs by developing a novel NOG substrain harboring a truncated version of the murine C3 gene (NOG-C3ΔMG2-3). Genetic C3 deletion prolonged the survival of transfused hRBCs in the circulation. Chemical depletion and functional impairment of mouse macrophages, using clodronate liposomes (Clo-lip) or gadolinium chloride (GdCl3), respectively, further extended the survival of hRBCs in NOG-C3ΔMG2-3 mice. Low GdCl3 toxicity allowed the establishment of hRBC-bearing mice, in which hRBCs survived for more than 4 weeks with transfusion once a week. In addition, erythropoiesis of human hematopoietic stem cells (hHSCs) was possible in NOG-C3ΔMG2-3/human GM-CSF-IL-3 transgenic mice with Clo-lip treatment. These findings indicate that mouse models harboring hRBCs can be achieved using NOG-C3ΔMG2-3 mice, which could facilitate studies of human diseases associated with RBCs.

scholarly journals Cytosolic ARFs are required for vesicle formation but not for cell-free intra-Golgi transport: evidence for coated vesicle-independent transport.

1994 ◽  
Vol 5 (2) ◽  
pp. 237-252 ◽  
Author(s):  
T C Taylor ◽  
M Kanstein ◽  
P Weidman ◽  
P Melançon
Keyword(s):  
Chinese Hamster Ovary ◽  
Chinese Hamster ◽  
Specific Inhibitor ◽  
Coated Vesicles ◽  
Coated Vesicle ◽  
Vesicle Formation ◽  
Golgi Transport ◽  
Independent Mechanism ◽  
Free Transport

We investigated the role of ADP-ribosylation factors (ARFs) in Golgi function using biochemical and morphological cell-free assays. An ARF-free cytosol produced from soluble Chinese hamster ovary (CHO) extracts supports intra-Golgi transport by a mechanism that is biochemically indistinguishable from control transport reactions: ARF-free transport reactions are NSF-dependent, remain sensitive to the donor Golgi-specific inhibitor ilimaquinone, and exhibit kinetics that are identical to that of control reactions containing ARFs. In contrast, ARF-free cytosol does not support the formation of coated vesicles on Golgi cisternae. However, vesicle formation is reconstituted upon the addition of ARF1. These data suggest that neither soluble ARFs nor coated vesicle formation are essential for transport. We conclude that cell-free intra-Golgi transport proceeds via a coated vesicle-independent mechanism regardless of vesicle formation on Golgi cisternae.

Nasopharyngeal reflexes: role of brain monoamines in central integration. a review

1988 ◽  
Vol 66 (1) ◽  
pp. 173-181
Author(s):  
Saxon White ◽  
Anthony Quail
Keyword(s):  
Functional Anatomy ◽  
Sympathetic Nerves ◽  
Lung Inflation ◽  
Independent Mechanism ◽  
Vagal Nerves ◽  
Intact Brain ◽  
Output Component ◽  
Trigeminal Nerves ◽  
Arterial Baroreceptor

The nasopharyngeal reflex in the rabbit (respiratory suppression, activation of vagal and sympathetic nerves, and reduction in oxygen usage) is initiated by trigeminal nerves and is enhanced by the arterial baroreceptor and by loss of lung inflation afferent activity. A review of (i) the functional anatomy of central nervous catecholamine and 5-hydroxytryptamine pathways participating in cardiorespiratory regulation, (ii) studies of the reflex in pontine, thalamic, and intact-brain rabbits in which the arterial baroreceptor and lung inflation inputs were manipulated, and (iii) studies of the reflex in rabbits in which central nervous catecholamine and 5-hydroxytryptamine were depleted indicates that the trigeminal nerve can initiate the reflex pattern during maintained ventilation at the ponto-medullo-spinal level through interactions that may include convergence with glossopharyngeal and vagal nerves in the nucleus of the solitary tract. By contrast, loss of lung inflation activity in itself activates vagal and sympathetic pathways through interactions with arterial baroreceptor activity and diencephalic influences. The vagal output component of the reflex is relatively independent of either central nervous monoamine, but the sympathetic vasoconstrictor component appears clearly dependent on central nervous catecholamine and, to a much lesser extent, on 5-hydroxytryptamine. Both monoamines play a role in respiratory suppression. Pentobarbitone blocks centrally the vagal output component of the nasopharyngeal reflex by a monoamine-independent mechanism. The findings provide a framework for testing postulates concerning central nervous catecholamine integration and neurotransmitter control of submergence reflexes in diving species.

Histochemistry of the Bucco-Oesophageal Glands of Mytilus Edulis: The Importance of Mucus in Ingestion

1993 ◽  
Vol 73 (1) ◽  
pp. 237-240 ◽  
Author(s):  
Peter G. Beninger ◽  
Marcel Le Pennec
Keyword(s):  
Mytilus Edulis ◽  
Digestive Enzymes ◽  
Blue Mussel ◽  
Suspension Feeding ◽  
Digestive Function ◽  
Acid Mucopolysaccharides ◽  
Secretory Gland ◽  
Particle Ingestion

Histochemical techniques were used to investigate the possible role of the buccooesophageal glands in the blue mussel, Mytilus edulis L. (Mollusca: Bivalvia). No activity was observed for any of the eight major digestive enzymes tested; however, the glands contained large amounts of both neutral and acid mucopolysaccharides. These results confirm the importance of mucus in the ingestive process in M. edulis, and do not support the hypothesis of ingestion of particles suspended in water alone.Until recently it was thought that the Bivalvia were the only class of molluscs in which some type of secretory gland of extracellular digestive function in the bucco-oesophageal region was totally absent (Table 1). However, in a study of the mode of particle ingestion in five species of suspension-feeding bivalves, an extensive glandular complex was reported in the bucco-oesophageal region of Mytilus edulis L. only (Beninger et al., 1991). Although these glands were observed to liberate secretions into the oesophageal lumen, it was not known whether they performed any digestive function.

Cyclooxygenase-independent mechanism of ibuprofen-induced antipyresis: the role of central vasopressin V1 receptors

2010 ◽  
Vol 25 (6) ◽  
pp. 670-681 ◽  
Author(s):  
Denis M. Soares ◽  
Rodrigo Cristofoletti ◽  
Miriam C. C. Melo ◽  
Charles J. Lindsey ◽  
Fabiane H. Veiga-Souza ◽  
...  
Keyword(s):  
Independent Mechanism
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