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At least 919 records · Page 51Linked to original sources
PubMed2001

Conserved role of a complement-like protein in phagocytosis revealed by dsRNA knockout in cultured cells of the mosquito, Anopheles gambiae.

We characterize a novel hemocyte-specific acute phase glycoprotein from the malaria vector, Anopheles gambiae. It shows substantial structural and functional similarities, including the highly conserved thioester motif, to both a central component of mammalian complement system, factor C3, and to a pan-protease inhibitor, alpha2-macroglobulin. Most importantly, this protein serves as a complement-like opsonin and promotes phagocytosis of some Gram-negative bacteria in a mosquito hemocyte-like cell line. Chemical inactivation by methylamine and depletion by double-stranded RNA knockout demonstrate that this function is dependent on the internal thioester bond. This evidence of a complement-like function in a protostome animal adds substantially to the accumulating evidence of a common ancestry of immune defenses in insects and vertebrates.

Animals↗
PubMed1999

Association of variants of the gene for mannose-binding lectin with susceptibility to meningococcal disease. Meningococcal Research Group.

BACKGROUND: The reasons why meningococcal disease develops in only a small proportion of individuals carrying the causative bacteria are unknown. Differences in host responses to bacterial colonisation are thought to be involved, since people with deficiencies in the terminal components of the complement pathway, or of properdin, are susceptible to meningococcal disease. We postulate that genetic variants of mannose-binding lectin (MBL), a plasma opsonin that initiates another pathway of complement activation, might similarly cause susceptibility to meningococcal disease. METHODS: The frequency of variants of the MBL gene was ascertained in children with meningococcal disease and controls from two independent studies; one hospital-based (194 patients and 272 controls [patients with non-infectious disorders]), and one community-based (72 patients and 110 controls [healthy individuals]), by means of PCR and restriction-enzyme digestion, with confirmation by DNA sequencing. FINDINGS: The proportion of people homozygous for MBL-variant alleles was higher in patients with meningococcal disease than in controls in the hospital study (15 [7.7%] vs four [1.5%]; odds ratio 6.5 [95% CI 2.0-27.2]) and in the community study (six [8.3%] vs three [2.7%]; 4.5 [0.9-29.1]). The population attributable fraction of cases attributable to MBL variants (homozygous and heterozygous) was 32%. INTERPRETATION: The MBL pathway is a critical determinant of meningococcal-disease susceptibility, and genetic variants of MBL might account for a third of all disease cases.

Adolescent↗
PubMed2002

The influence of plasma proteins and platelets on oxygen radical production and F-actin distribution in neutrophils adhering to polymer surfaces.

It is well known that blood cell interactions with artificial surfaces might have deleterious effects on host tissue, however, the mechanisms involved are far from understood. In this study, neutrophil-platelet interaction on uncoated or protein-coated polymer surfaces was investigated. Cell spreading, reorganization of actin filaments and release of oxygen metabolites (measured as luminol-amplified chemiluminescence) were used as criteria for cell activation on positively charged, hydrophilic 1,2-diaminocyclohexane, and negatively charged, hydrophobic hexamethylene-disiloxane. The model surfaces were made by radio frequency plasma discharge polymerization. Neutrophil contact with the uncoated polymers induced a prolonged generation of oxygen radicals. Precoating of the polymer surfaces with human serum albumin (HSA) or fibrinogen, markedly reduced neutrophil activation, whereas coating with human immunoglobulin G (IgG), a well-known opsonin, resulted in significantly higher levels of cell activation. Consequently, protein coating overruled the activating effects of the polymer surfaces. The presence of unstimulated or thrombin-stimulated platelets markedly increased the reactivity of neutrophils against fibrinogen- and IgG-coated surfaces. However, neutrophils remained relatively unreactive in the presence of platelets on HSA-treated surfaces. Comparison of the different types of surfaces used, reveals a correlation between the degree of cell spreading, reorganization of the actin cytoskeleton and the amount of oxygen radicals produced. Our results suggest that the acute inflammatory reaction on a biomaterial surface is highly dependent on the nature and composition of the first adsorbed protein layer and the extent of platelet activation.

Actins↗
PubMed1998

Ribosomal proteins sustain morphology, function and phenotype in acute myeloid leukemia blasts.

Translation of mRNA is a prerequisite for cell proliferation, differentiation and viability. We have studied the effect of ribosome protein factors (GPRE) on acute myeloid leukemia (AML) blast cells. Ribosomes were isolated from MPC-11 cells using ultra-centrifugation. GPRE were extracted using a high KCl procedure. Blast cells from six AML patients were grown in suspension cultures for 24 and 96 h. GPRE or granulocyte macrophage-colony stimulating factor (GM-CSF) were added at the start of the incubation. GPRE, but not GM-CSF, prevented chromatin condensation and fragmentation of blast cell nuclei in AML-M2, -M4 and -M5 and the loss of nucleoli in AML-M2 and -M5. The fraction of phagocytosing blast cells in AML-M1, -M2, -M4 and -M5 was increased by GPRE. GPRE stimulated opsonin-dependent and -independent attachment and internalisation of N. meningitidis. GPRE increased the fraction of blasts expressing CD11b and CD32 in AML-M2 and -M5. GPRE diminished the fraction of AML-M5 cells bearing CD35 and CD32. GPRE also decreased the fraction of CD11c-bearing AML-M2 and -M5 cells. GM-CSF potentiated effects of GPRE in AML-M1, -M2, -M4 and -M5. GPRE and GM-CSF in combination affected phagocytosis and surface antigen expression in blast cells that were not influenced by either factor alone. Neither GPRE nor GM-CSF induced terminal differentiation or DNA-synthesis. We conclude that GPRE affects AML blast cell morphology, function and surface molecule expression, possibly by inhibiting apoptosis. The effects of GPRE may be mediated by ribosomal proteins that regulate translation and modulate the subcellular distribution of mRNA species.

Acute Disease↗
PubMed2002

Thioester function is conserved in SpC3, the sea urchin homologue of the complement component C3.

The amino acid sequence of the thioester site in the alpha chain of SpC3, the sea urchin homologue of C3, is conserved. This implies a conserved function of covalent bond formation with amine or hydroxyl groups on target molecules. When coelomic fluid (CF) was incubated with 14C-methylamine, a classic assay for thioester binding function, the alpha chain became labeled. When CF was treated to induce autolysis, peptide bond cleavage occurred at the thioester site. Autolysis could be blocked or reduced by pre-treating CF with either methylamine or yeast, both of which are known to bind to thioester sites C3 proteins from other organisms. The data suggest that SpC3 can bind to target cell surfaces, constituting indirect evidence that it can covalently bind to pathogen surfaces and function as an opsonin in vivo. This activity may be an important aspect of host defense in the sea urchin.

Amino Acid Sequence↗
PubMed2001

Human C-reactive protein: expression, structure, and function.

C-reactive protein (CRP) is an acute-phase protein featuring a homopentameric structure and Ca-binding specificity for phosphocholine (PCh). Expression of CRP is regulated mainly at the transcriptional level with interleukin-6 being the principal inducer of the gene during the acute phase. The crystal structure of CRP has been determined and the topology and chemical composition of its ligand-binding site determined. The wide distribution of PCh in polysaccharides of pathogens and in cellular membranes allows CRP to recognize a range of pathogenic targets as well as membranes of damaged and necrotic host cells. CRP bound to a multivalent ligand can efficiently initiate the assembly of a C3 convertase through the classical pathway and thus decorate the surface of the ligand with opsonic complement fragments. However, the protein does not favor the formation of a C5 convertase and therefore, CRP-initiated complement activation does not mediate acute inflammatory reactions and membrane damage. CRP also interacts with Fc receptors on phagocytic cells and acts as an opsonin. Other CRP-initiated signals through interactions with neutrophil Fc receptors have an overall anti-inflammatory effect. Thus, the main biological function of CRP appears to be host defense against bacterial pathogens and clearance of apoptotic and necrotic cells. Protection from lethal bacterial infection, from complement-induced alveolitis, and from endotoxemia has been confirmed in vivo using transgenic mice. Additional functions, including participation in atherogenesis and pathogenesis of myocardial injury after myocardial infarction have been reported. However, the weight of the evidence is that CRP like other acute-phase proteins is a component first line of innate host defense.

C-Reactive Protein↗
PubMed2002

Novel characterisation of the gene encoding conglutinin reveals that previously characterised promoter corresponds to the CL-43 promoter.

Conglutinin, a collectin found in bovine serum, is an opsonin that binds to glycoconjugates on the surface of microorganisms or on deposited iC3b, and acts in concert with phagocytes to establish a first-line of immune defense. We have isolated a genomic conglutinin phage clone and found that the 5'-flanking region shows 95.8% identity with the sequence previously published, which on the other hand shows 99.7% identity with the CL-43 promoter. We conclude that the previously published promoter corresponds to the CL-43 promoter and that the functional studies performed on it apply to transcription of CL-43. Comparison of potential cis-regulatory elements in relation to the functional studies indicates that the two genes are regulated by different mechanisms.

Base Sequence↗
PubMed2001

IgM detection via selective recognition by mannose-binding protein.

Ca(2+)-dependent mannose-binding proteins (MBPs) belong to the family of animal lectins isolated from the liver and serum of rabbits, humans and rodents. They perform in vivo as defense molecules that act as opsonins by enhancing the clearance of mannose-rich pathogens and have been used in vitro for the purification of immunoglobulin M (IgM). In this study, we used MBPs as a sensitive and specific reagent for the detection of IgM due to their high specificity for mannose found only in IgM carbohydrate regions. MBP performed as a sensitive alternative to the usually used anti-IgM, where very low concentrations of IgM should be detected. IgM plays a central role in the initial response of the immune system to the invasion of foreign pathogens, as the early detection of the appearance of pathogenic IgM in biological fluids is of great significance in the diagnosis and treatment of many acute pathological cases. The development of a highly sensitive and reliable assay for the detection of low concentrations of IgM based on covalent binding on epoxy film-coated surfaces and selective recognition of IgM by MBP may be of clinical importance.

Animals↗
PubMed1998

Evaluation of neutrophilic function (chemotaxis, phagocytosis and microbicidal activity) in healthy dogs and in dogs suffering from recurrent deep pyoderma.

The modified Boyden's technique of chemotaxis ('leading front' method) and the bacterial killing test with Staphylococcus sp. stained with acridine orange were performed with suspensions of granulocytes from 50 healthy dogs. Lipopolisacharide of Escherichia coli, in normal dog serum was used as the chemotactic factor. The mean value for the chemotactic differential found was 30.41 +/- 12.14 mu. The optimal concentration of bacteria and opsonins (normal dog serum) was 4 and 15%, respectively, and the ideal incubation period was 30 min. The mean values obtained for phagocytosis percentage, number of bacteria per PMN, phagocytosis index and percentage of dead bacteria, were 97.01 +/- 3.22%, 22.20 +/- 4.6, 21.53 +/- 4.50 and 45.30 +/- 9.18%, respectively. Granulocyte functions in 18 dogs with recurrent, chronic, deep pyoderma were assessed by the same methods. No significant difference between the two groups, for any of the evaluated parameters, was found. For elucidation of the pathogenesis of recurrent pyoderma, further studies involving humoral and cellular immunity and the complement system are required.

Animals↗
PubMed1999

Serum levels of chicken mannan-binding lectin (MBL) during virus infections; indication that chicken MBL is an acute phase reactant.

Mannan-binding lectin (MBL) is a serum collectin which is believed to be an opsonin of the innate immune defence against various microorganisms. MBL is a minor acute phase reactant in man. We investigated the concentration of serum MBL in chickens infected with infectious bronchitis virus (IBV) and infectious laryngotracheitis virus (ILTV). The concentration of serum MBL increased about twofold (from approximately 6 to 12 microg/ml) due to these viral infections. The concentration peaked 3-7 days after infection with IBV, and 3-5 days after ILTV infection, depending on the ILTV strain used. The increased levels returned to normal values 6-10 days after infection. The results indicated that MBL is a minor acute phase reactant in chickens.

Animals↗
PubMed1998

Receptor versus non-receptor mediated clearance of liposomes.

Numerous studies have appeared over the years dealing with liposome-cell interaction mechanisms, most of them performed under in vitro conditions with isolated cell populations or cell lines. It is remarkable that, nonetheless, there hardly seem to exist established and generally accepted views on how precisely liposomes interact with cells and by what parameters this is influenced. In this article we will summarize and discuss the most relevant studies (in our opinion) on this matter in relation to in vivo conditions and with special attention to the relation between scavenger, complement and PS receptors.Researchers in the field have long been aware of the interaction of liposomes with blood proteins and their potential involvement in the process of liposome elimination from the blood circulation. A few of these 'opsonizing' proteins have been identified, but it is not clear to what extent each of them determines the fate of the liposome in the blood stream and how liposomal parameters such as size, charge and rigidity play a role in this process. We will include in this article our own recent observations on a thus far largely ignored class of such liposomal 'opsonins', the apolipoproteins. This class of plasma proteins, which physiologically are instrumental in hepatic lipoprotein clearance and processing, has been shown to contribute specifically to hepatocyte-mediated uptake of liposomes.Separately, as opposed to the fate of plain liposomes, we briefly touch on the clearance of surface-modified liposomes, which are designed to actively target specific cells or tissues. Plasma proteins are not usually supposed to play a significant role in the clearance of such liposomes. We will summarize these studies and address in this connection the question of how plasma proteins may interfere with such active targeting attempts.

Journal Article↗
PubMed1982

Comparative phagocytosis of cadmium microcrystals by peripheral blood glass-adherent cells of newborn and healthy adults.

Microcrystals of cadmium, saturated with human serum albumin, were employed as a microassay for phagocytosis by glass-adherent blood cells. Using this assay, it was found that leukocytes of newborns possess significantly higher phagocytic activity and that a higher proportion of active phagocytic cells is present in newborns than in adults. In contrast, adult sera contain higher level of opsonins for cadmium microcrystals than cord sera. Heat inactivation and zymosan absorption of both adult and cord sera decreased significantly the opsonic power of sera, thus suggesting the participation of complement in opsonization of these particles.

Adult↗
PubMed1988

Cell surface antigen of encapsulated Staphylococcus epidermidis SE-360 protects mice from homologous infection.

Cell surface antigen was mechanically extracted from encapsulated strain SE-360 of Staphylococcus epidermidis and purified by DEAE-Sephadex A 25 (Cl- form) ion exchange chromatography. This antigen manifested type-specific activity and major sugar constituents were galactose, glucose and N-acetyl-glucosamine at the molar ratio 1.00:9.05:1.65. alpha-D-glucosyl- and N-acetyl-glucosaminyl-residues were closely correlated to the antigenic determinant. In mice, protection against homologous microorganisms could be achieved by active immunization with thus purified antigen. Type-specific opsonin in rabbit anti-SE-360 serum could also be absorbed.

Animals↗
PubMedDate not supplied

Microglial chemotaxis, activation, and phagocytosis of amyloid beta-peptide as linked phenomena in Alzheimer's disease.

Microglia are widely held to play important pathophysiologic roles in Alzheimer's disease (AD). On exposure to amyloid beta peptide (A beta) they exhibit chemotactic, phagocytic, phenotypic and secretory responses consistent with scavenger cell activity in a localized inflammatory setting. Because AD microglial chemotaxis, phagocytosis, and secretory activity have common, tightly linked soluble intermediaries (e.g., cytokines, chemokines), cell surface intermediaries (e.g., receptors, opsonins), and stimuli (e.g., highly inert A beta deposits and exposed neurofibrilly tangles), the mechanisms for microglial clearance of A beta are necessarily coupled to localized inflammatory mechanisms that can be cytotoxic to nearby tissue. This presents a critical dilemma for strategies to remove A beta by enhancing micoglial activation--a dilemma that warrants substantial further investigation.

Alzheimer Disease↗
PubMedDate not supplied

Molecular and cellular characterization of the membrane attack complex, C5b-9, in Alzheimer's disease.

The membrane attack complex, C5b-9, is of considerable importance in many inflammatory reactions. It is the terminal, cytolytic component of both classical and alternative pathway activation, and its presence presupposes other potentially destructive complement constituents, including anaphylotoxins and opsonins. We have characterized C5b-9 and its C9 constituent in the Alzheimer's disease (AD) and nondemented elderly (ND) brain using immunohistochemistry at the light and electron microscopic levels, Western blot analysis, and the reverse transcriptase polymerase chain reaction. We have also conducted in vitro ELISA assays of amyloid beta-peptide-stimulated SC5b-9 production. C5b-9 is abundantly present in Alzheimer's disease cortex, associated with neurofibrillary tangle containing neurons, dystrophic neurites within neuritic plaques, and neuropil threads, but is weakly detected, if at all, in nondemented elderly cortex under the same conditions. Staining of Alzheimer's disease sections is abolished both by deletion of primary antibody or preabsorption with purified SC5b-9.

Alzheimer Disease↗
PubMed2001

Qualitative assessment of the humoral immune status against FMDV in post-vaccination cattle.

Analyses on diluted sera would not measure the complete activity of the natural in-vivo serum environment used by humoral immune responses. Since these humoral defences must react rapidly, serum reactions occurring during 10 and 60 s were analysed. Primo- and multiple-vaccinated, efficiently responsive, and protected animals were differentiated. A variation in the responses, particularly the quality of response, of individual animals was also now discernible. The critical importance of antibody-antigen contact time was demonstrated, wherein natural immunoglobulins and non-immunoglobulin opsonins would influence specific antibody reactivity, through an increased avidity of reaction with antigen. Although not measured directly, the influence of the non-specific serum components would be manifest through increased specific antibody binding. By considering serum as an entity, analysis of all constituent components permits increased qualitative assessment of post-vaccination sera.

Age Factors↗
PubMed1987

Neutrophil and monocyte alterations in chronic dialysis patients.

Chronic renal failure patients maintained on dialysis have an increased risk for infection. This article summarizes research that has been done on the function of neutrophils (PMNs) and monocytes from chronic hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) patients. The studies involving the HD patients showed that there is a decreased PMN in vitro chemotactic response, decreased C5a receptors on both PMNs and monocytes, and decreased oxidative metabolic responses of PMNs and monocytes to the chemotactic stimuli C5a and formyl-met-leu-phe (fMLP), but not to nonchemotactic factors. The results of studies involving phagocytosis have been conflicting and are discussed in this paper. Due to the basic principles of peritoneal dialysis, this treatment approach depletes the peritoneum of phagocytic cells, adversely affects the function of peritoneal WBCs, dilutes the existing opsonins, and alters the physiologic environment of the peritoneal cavity. Studies of peripheral PMN and monocyte function in CAPD patients have shown that, similar to HD patients, they also have decreased C5a receptors and decreased oxidative metabolic responses to the chemotactic factors C5a and fMLP. Although the factors contributing to the risk of infection in chronic dialysis patients are multifaceted, there are definitely alterations in PMN and monocyte function.

Disease Susceptibility↗