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At least 793 records · Page 44Linked to original sources
PubMed1992

Adherence of Legionella pneumophila to guinea pig peritoneal macrophages, J774 mouse macrophages, and undifferentiated U937 human monocytes: role of Fc and complement receptors.

Legionella pneumophila, the causative agent of Legionnaires' disease, is a facultative intracellular pathogen of alveolar macrophages. Although previous studies have demonstrated that specific antibody facilitates uptake of L. pneumophila by phagocytic cells, the role of complement has been unclear. Thus, we have examined the relative contributions of Fc gamma- and complement receptor-mediated adherence to guinea pig peritoneal macrophages, U937 human monocytic cells, and J774 mouse macrophage cells. Opsonization of L. pneumophila (Philadelphia 2) with polyclonal immunoglobulin G promoted maximum adherence to guinea pig macrophages. In contrast, incubation in the presence of 20% fresh nonimmune human serum from a single donor did not promote adherence. The results obtained with U937 and J774 cells paralleled those obtained with guinea pig macrophages. In the absence of specific antibody, opsonization with guinea pig complement did not enhance adherence of the Philadelphia 1, Philadelphia 2, or Knoxville strain. However, when complement was added to heat-inactivated, specific antiserum, a fourfold increase in the number of adherent organisms was observed. Blocking studies utilizing membrane receptor-specific monoclonal antibodies demonstrated that both Fc and complement receptors mediated adherence of organisms treated with complement in the presence of specific antibody. These results suggest that complement augments adherence of L. pneumophila only when acting in concert with specific antibody.

Animals↗
PubMed1977

Expression of Fc and complement receptors on T lymphocytes activated in vitro by phytohaemagglutinin (PHA).

In this work T-enriched lymphocyte populations (obtained from Ig-anti-Ig-Degalancoated columns) were studied for their surface markers, especially for Fc and complement receptors, before and after a pulse-PHA-stimulation. It has been demonstrated that activated T lymphocytes express on their surface both of these markers in high percentage. The hypothesis is discussed that B and T lymphocytes differ only with regard to the presence of surface immunoglobulins or the ability of forming spontaneous rosettes. On the contrary the other surface markers may probably be expressed when needed functionally by the cells.

Adult↗
PubMed1999

Complement receptor type 3 plays an important role in development of protective immunity to primary and secondary Corynebacterium pseudotuberculosis infection in mice.

The present study was performed to investigate the role of CR3, the type 3 complement receptor, in host defense against primary and secondary Corynebacterium (C.) pseudotuberculosis infection in mice. Treatment of mice with 5C6, an anti-CR3 monoclonal antibody (mAb), resulted in unrestricted multiplication of bacteria in the organs and dramatically increased mortalities of the infected mice. Histological examinations showed the inflammation, degeneration and necrosis of organs and revealed that the infection-enhancing effect of 5C6 mAb was associated with the failure of mice to focus mononuclear phagocytes at sites of bacterial multiplication. These results suggest that CR3 plays an important role in host defense against primary as well as secondary C. pseudotuberculosis infection in mice.

Animals↗
PubMed2005

Absence of complement receptor 3 results in reduced binding and ingestion of Mycobacterium tuberculosis but has no significant effect on the induction of reactive oxygen and nitrogen intermediates or on the survival of the bacteria in resident and interferon-gamma activated macrophages.

The interaction of host macrophage (Mphi) and Mycobacterium tuberculosis (Mtb) is mediated by cell surface receptors and is important in establishing intracellular infection. Mphis can kill invading organisms via reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI). Using a Complement Receptor 3 (CR3) knockout mouse model we have examined whether the presence of CR3 affects the binding and uptake of viable Mtb by Mphis, the survival of the ingested bacteria and the induction of ROI and RNI during this interaction. We show that, although CR3 plays a role in the uptake of viable Mtb, the receptor plays no role in the subsequent survival of the bacteria. The finding holds true for resident Mphis and for interferon-gamma (IFN-gamma) activated Mphis, both in the absence and presence of serum opsonins. Activation of Mphi populations with IFN-gamma significantly inhibits the growth of Mtb in host Mphis and enhances the production of ROI and RNI. However, the presence of CR3 was not critical in any of these mechanisms. Furthermore, we demonstrate that the control of intracellular growth of Mtb in IFN-gamma activated Mphis is not mediated by a direct effect of RNI.

Animals↗
PubMed1993

Very late antigen-5 and complement receptor type 3 cooperatively mediate the interaction between Bordetella pertussis and human monocytes.

Nonopsonized Bordetella pertussis, the causative agent of whooping cough, can attach to and become ingested by human monocytes. It has been reported that complement receptor type 3 (CR3) on human monocyte-derived macrophages binds filamentous hemagglutinin expressed on B. pertussis. In the present study, the role of very late antigen-5 (VLA-5) in the attachment of B. pertussis to adherent human monocytes was investigated. It was found that soluble fibronectin and soluble mAb against VLA-5 markedly inhibited the attachment of B. pertussis to monocytes. When VLA-5 on monocytes was cross-linked by plating these cells onto surfaces precoated with fibronectin or mAb against VLA-5, the binding of both B. pertussis and C3bi-coated sheep erythrocytes to these cells was significantly enhanced, whereas the binding of a B. pertussis mutant strain deficient in filamentous hemagglutinin was not affected. The enhanced attachment of B. pertussis to monocytes plated onto fibronectin-coated surfaces was markedly inhibited by soluble mAb against CR3. Neutrophils, which express similar levels of CR3 and about 10-fold lower levels of VLA-5 as compared with monocytes, did not bind B. pertussis. Together, these results indicate that VLA-5 is involved in the attachment of B. pertussis to monocytes and that cross-linking of VLA-5 enhances the attachment of B. pertussis to monocytes by augmenting the binding activity of CR3. We propose that the attachment of B. pertussis to monocytes occurs in two steps: binding and cross-linking of VLA-5 by B. pertussis enhances the binding activity of CR3, which in turn facilitates the subsequent binding of these bacteria to the latter receptor.

Adhesins, Bacterial↗
PubMed1994

Granulocyte-macrophage colony-stimulating factor, interleukin-3 (IL-3), and IL-5 greatly enhance the interaction of human eosinophils with opsonized particles by changing the affinity of complement receptor type 3.

Eosinophil functions can be modulated by several cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-5. We have investigated the modulatory role of these cytokines on the interaction of human eosinophils with opsonized particles (serum-treated zymosan [STZ]). Addition of STZ to eosinophils isolated from the peripheral blood of normal human donors resulted in an interaction of the STZ particles with only 15% to 25% of the cells. Treatment of the eosinophils with GM-CSF, IL-3, or IL-5 strongly enhanced both the rate of particle binding and the percentage of eosinophils binding STZ. The effect of the cytokines is most likely mediated by a change in affinity of the complement receptor type 3 (CR3) on the eosinophils for the complement fragment iC3b on the STZ particles. This is indicated by the observation that (1) the effect of the cytokines on STZ binding was prevented by a monoclonal antibody against the iC3b-binding site on CR3 and (2) the enhanced binding was already apparent before upregulation of CR3 on the cell surface was observed. In a previous study, similar results were obtained with platelet-activating factor (PAF)-primed eosinophils. Because we found that the cytokines strongly enhanced the STZ-induced PAF synthesis, we investigated the role of both released PAF and cell-associated PAF in the priming phenomenon by the cytokines. Cytokine priming appeared to be largely independent of the synthesis of PAF.

Eosinophils↗
PubMed1995

Investigation of the complement receptor 3 (CD11b/CD18) in human rectal epithelium.

Rectal and cervicovaginal mucosa are common routes of transmission of HIV, although the mechanism of transmission is unknown. We have investigated human rectal and cervicovaginal epithelia for the expression of complement receptors (CR) and cell adhesion molecules which may be involved in HIV and other infections. In rectal mucosa, CR3 was detected in the surface and crypt epithelial cells by immunohistology, using MoAbs to CD18 and CD11b in 10 out of 15 specimens. RNA transcripts encoding both CD11b and CD18 were also demonstrated in surface and crypt epithelial cells by in situ hybridization. Although CD11b was detected in the epithelial cells in three out of the 14 cervicovaginal specimens, we were unable to detect CD18. We suggest that expression of the CD11b/CD18 heterodimer might facilitate transmission of HIV by enhancing binding of HIV-antibody complexes in seminal fluid to epithelial cells. Alternatively, since intercellular adhesion molecule-1 (ICAM-1) is a receptor for CD11b/CD18, this may promote adhesion between epithelial cells and HIV-infected mononuclear cells in seminal fluid.

CD18 Antigens↗
PubMed1995

Granulocyte activation via a binding site near the C-terminal region of complement receptor type 3 alpha-chain (CD11b) potentially involved in intramembrane complex formation with glycosylphosphatidylinositol-anchored Fc gamma RIIIB (CD16) molecules.

We report that engagement of a particular epitope near the C-terminal region of complement receptor type 3 (CR3, CD11b/CD18) alpha-chain with CD11b mAb VIM12 induces granulocyte activation with a rise in cytosolic-free Ca2+, actin polymerization, an up-regulation of CR3 cell surface expression and enhanced adhesiveness. Induction of enhanced adhesiveness and homotypic aggregation of human granulocytes represents an active process. It is temperature and energy dependent, requires divalent cations, and an intact cytoskeleton. The mAb VIM12-induced enhanced adhesiveness seems to be mediated, at least in part, by activated CR3 molecules. It can be significantly inhibited, although not completely abolished, with blocking mAbs against adhesiotopes of CR3. VIM12-induced adhesion could be blocked with the serine/threonine inhibitors okadaic acid and calyculin A and with dibuturyl-cAMP but not with the protein kinase inhibitors herbimycin A and staurosporine. We further present evidence that the particular molecular region of CR3 recognized by mAb VIM12 might be involved in the reported intramembrane sugar-lectin type interaction and complex formation between transmembrane CR3 and glycosylphosphatidylinositol (GPI)-anchored Fc gamma RIIIB (CD16) molecules on human granulocytes. Binding of mAb VIM12 to CR3 on granulocytes enhances the release of GPI-anchored Fc gamma RIIIB molecules from granulocytes upon phosphoinositol-phospholipase C treatment. The sugar preparation N-acetyl-D-glucosamine, previously shown to dissociate CR3-Fc gamma RIIIB complex formation, inhibits mAb VIM12 binding. Engagement of CR3 with mAb VIM12 may thus mimic a biologically relevant intramembrane cooperation between two distinct receptor molecules on human granulocytes.

Actins↗
PubMed1997

Interaction of GPI-anchored cell surface proteins and complement receptor type 3.

Glycosylphosphatidylinositol (GPI)-anchored cell surface proteins lack transmembrane and cytoplasmic domains. For some of them, such as CD14, CD16b and CD87, it could be demonstrated recently that they are physically and functionally associated with complement receptor type 3 (CR3, CD11b/CD18). Also, there are indications that in certain cells these GPI proteins employ CR3 as an adapter for signal transduction across the plasma membrane.

Antigens, CD↗
PubMed1987

Activation of mouse peritoneal macrophages by monoclonal antibodies to Mac-1 (complement receptor type 3).

Several features of activation of mouse peritoneal macrophages were elicited by 1-2-d exposure to submicrogram concentrations of anti-Mac-1 (M1/70), a rat monoclonal antibody that reacts with the alpha chain of complement receptor type 3 (Mac-1). The changes induced included enhanced capacity to secrete H2O2 when triggered with PMA, decreased secretion of proteins, increased expression of Ia antigen and decreased phagocytosis of particles. These changes closely resembled those induced by rIFN-gamma in type, extent, and time course. The concentration of M1/70 IgG resulting in 50% of the maximal activation of macrophage H2O2-releasing capacity averaged 0.18 +/- 0.03 micrograms/ml. This activation was not blocked by anti-FcR mAb, and could be reproduced with M18/2, a mAb against beta chain of Mac-1, suggesting that a direct ligation of Mac-1 with mAb was responsible for the activation. Neither depletion of T cells nor addition of neutralizing Abs to IFN-gamma or TNF-alpha prevented M1/70-mediated macrophage activation. Moreover, F(ab')2 of M1/70, or plating of macrophages on C3bi-coated surfaces, inhibited the activation of macrophages by rIFN-gamma. These findings suggest that Mac-1 (CR3) may play an important role in macrophage activation.

Animals↗
PubMed1990

Structural and functional correlation of the human complement receptor type 1.

Human CR1 is widely distributed in the circulation as a surface receptor as well as in soluble form in the plasma. It mediates a variety of functions that include phagocytosis and regulation of the complement cascade. This receptor has been cloned and the primary structure reveals that the cell-bound molecule is an integral membrane protein with typical transmembrane and cytoplasmic domains. Its extracellular portion is composed entirely of 30 short consensus repeats (SCR) each having 60 to 70 amino acids. This type of motif is the common structural element of the superfamily of complement regulatory and receptor proteins on chromosome 1. The amino-terminal 28 SCR of CR1 is uniquely organized into four tandem long homologous repeats (LHR) with sequence homologies among corresponding SCR as high as 99%. Each LHR encodes approximately 45 kD and each except the one that is proximal to the cell surface contains a separate binding site for C3b or C4b. Analysis of the genomic structure of CR1 reveals that these LHR are results of intragenic duplication of 20- to 30-kb segments of DNA. The structural allotypes of CR1 that vary in the lengths of the polypeptides are encoded by alleles that contain different numbers of LHR. Their predicted structures would have different numbers of C3b binding sites, perhaps resulting in molecules with different capacities to bind immune complexes.

Alleles↗
PubMed2005

A role for mammalian diaphanous-related formins in complement receptor (CR3)-mediated phagocytosis in macrophages.

Macrophages, dendritic cells, and neutrophils use phagocytosis to capture and clear off invading pathogens. The process is triggered by the interaction of ligands on the pathogens' surface with specific phagocytic receptors, including immunoglobulin (FcR) and complement C3bi (CR3) receptors (integrin alpha(M)beta2, Mac1) . Localized actin-filament assembly that acts as the driving force for particle engulfment is controlled by Rho-family small GTPases . RhoA regulates CR3-mediated phagocytosis through a mechanism that is still unclear . Mammalian Diaphanous-related (mDia) formins participate in the generation of a diverse set of actin-remodeling events downstream of RhoA , and mDia1 is recruited around fibronectin-coated beads in a RhoA-dependent manner in fibroblasts . Here, we set out to examine whether mDia proteins are involved in CR3-mediated phagocytosis in macrophages. We show that the RhoA effector mDia1 is recruited early during CR3-mediated phagocytosis and colocalizes with polymerized actin in the phagocytic cup. Interfering with mDia activity inhibits CR3-mediated phagocytosis while having no effect on FcR-mediated phagocytosis. These results indicate a new function for mDia proteins in the regulation of actin polymerization during CR3-mediated phagocytosis.

Actins↗
PubMed1985

Erythrocyte enhancement of C3b-mediated phagocytosis by human neutrophils in vitro: a combined effect of the erythrocyte complement receptors CR1 and erythrocyte scavengers to reactive oxygen metabolites (ROM).

Human erythrocyte CR1 receptors have been shown to bind complement-fixing immune complexes and, thus, facilitate their elimination from the circulation. The autotoxic effect of free radicals released from phagocytes during phagocytosis can be alleviated by scavengers like catalase and superoxide dismutase. Erythrocytes are known to contain these antioxidants. This study showed that 74% of opsonized yeast particles adhered to human erythrocytes. No difference was seen between yeast opsonized with C3b and yeast opsonized with both IgG and C3b. This adherence was due to the C3b receptor (CR1), as monoclonal antibodies against the CR1 receptor could abrogate the adherence. The yeast phagocytosis by neutrophils was increased by 15% when yeast-C3b was used, and by 34% when yeast-IgG/C3b was used in the presence of human red blood cells. The increase of phagocytosis was not seen when rat erythrocytes (lacking CR1) were present. The cytochrome c reduction decreased with the presence of human erythrocytes during phagocytosis, indicating a scavenging effect on the superoxide anions. The addition of scavengers or erythrocyte lysate, instead of erythrocytes, enhanced phagocytosis of yeast-IgG/C3b to at least the same extent as the erythrocytes. These observations suggest that human erythrocytes primarily enhance phagocytosis through the scavenging effect of those erythrocytes which are concurrently attached with the prey through its CR1 receptor, and then attached to the PMN.

Complement C3b↗
PubMed2005

Complement receptors regulate differentiation of bone marrow plasma cell precursors expressing transcription factors Blimp-1 and XBP-1.

Humoral immune responses are thought to be enhanced by complement-mediated recruitment of the CD21-CD19-CD81 coreceptor complex into the B cell antigen receptor (BCR) complex, which lowers the threshold of B cell activation and increases the survival and proliferative capacity of responding B cells. To investigate the role of the CD21-CD35 complement receptors in the generation of B cell memory, we analyzed the response against viral particles derived from the bacteriophage Qbeta in mice deficient in CD21-CD35 (Cr2(-/-)). Despite highly efficient induction of early antibody responses and germinal center (GC) reactions to immunization with Qbeta, Cr2(-/-) mice exhibited impaired antibody persistence paralleled by a strongly reduced development of bone marrow plasma cells. Surprisingly, antigen-specific memory B cells were essentially normal in these mice. In the absence of CD21-mediated costimulation, Qbeta-specific post-GC B cells failed to induce the transcriptional regulators Blimp-1 and XBP-1 driving plasma cell differentiation, and the antiapoptotic protein Bcl-2, which resulted in failure to generate the precursor population of long-lived plasma cells residing in the bone marrow. These results suggest that complement receptors maintain antibody responses by delivery of differentiation and survival signals to precursors of bone marrow plasma cells.

Allolevivirus↗
PubMed2003

Coxiella burnetii avoids macrophage phagocytosis by interfering with spatial distribution of complement receptor 3.

Phagocytosis is a highly localized event requiring the formation of spatially and temporally restricted signals. Numerous microorganisms have taken advantage of this property to invade host cells. Coxiella burnetii, the agent of Q fever, is an obligate intracellular bacterium that has developed a survival strategy in macrophages based on subversion of receptor-mediated phagocytosis. The uptake of C. burnetii is mediated by alpha(v)beta(3) integrin and is restricted by impaired cross-talk of alpha(v)beta(3) integrin and complement receptor 3 (CR3) (CD11b/CD18). In this study, we showed that CR3 molecules remained outside the pseudopodal extensions induced by C. burnetii in THP-1 monocytes, although alpha(v)beta(3) integrin was present in the pseudopods. Chemoattractants such as RANTES restored CR3 localization to the front of pseudopodal extensions and increased C. burnetii phagocytosis, demonstrating that the localization of CR3 is critical for bacterial uptake. In addition, monocyte activation due to the expression of HIV-1 Nef protein also restored CR3-mediated phagocytosis of C. burnetii by allowing CR3 redistribution toward bacterial-induced pseudopods. The redistribution of CR3 and increased C. burnetii phagocytosis in THP-1 cells stimulated by RANTES or expressing Nef were associated with the inhibition of intracellular replication of C. burnetii. Hence, the localization of CR3 is critical for bacterial phagocytosis and also for the control of bacterial replication. This study describes a nonpreviously reported strategy of phagocytosis subversion by intracellular pathogens based on altered localization of monocyte receptors.

Animals↗
PubMed1997

Complement coating of erythrocytes is reduced following their interaction with neutrophils in vitro without loss of complement receptor 1 (CR1).

We have investigated the interaction of complement-coated erythrocytes (E) with neutrophils, in vitro, to determine the effects of erythrocyte CR1. Complement-coating in vitro, to mimic immune complex uptake, caused a reduction in E-CR1, but subsequent interaction with neutrophils effected a removal of E-C3b and a return of E-CR1 to levels approximating that of uncoated erythrocytes. These data indicate that C3b, associated with immune complexes, may bind to E-CR1 in a reversible manner and that subsequent interaction with phagocytes need not necessarily result in cleavage (and loss of) E-CR1. Further, we conclude that E-CRI can apparently be reduced by epitope masking.

Antigen-Antibody Complex↗
PubMed1994

Interactions of human complement component C3 with factor B and with complement receptors type 1 (CR1, CD35) and type 3 (CR3, CD11b/CD18) involve an acidic sequence at the N-terminus of C3 alpha'-chain.

Complement component C3 is a multifunctional protein that interacts with many different ligands and receptors. Several experimental approaches involving blocking Abs, proteolytic fragmentation, and synthetic peptides have been used to predict which regions in C3 are required for its various functions. We have used site-directed mutagenesis to alter specific residues in the C3 segments 730-739 and 933-942 that have been proposed to be required for the binding of factor B by C3, and have examined, within the context of the intact C3b molecule, the effect of these substitutions on the C3b-factor B interaction. Because it has been suggested that factor H and complement receptors type 1, 2, and 3 may recognize sites in C3 that partially or completely overlap those of factor B, the relevant proteolytic fragment of each mutant C3 was tested for its ability to interact with these molecules. This study clearly demonstrates that a segment near the N-terminus of the alpha'-chain, which contains the negatively charged residues 730DE and 736EE, is involved in the interactions of C3 proteolytic fragments with factor B and complement receptors type 1 and 3, but not type 2. Factor H cofactor activity was also partially affected by these mutations. In contrast, mutation of the 937KED triplet in the C3 933-942 segment had little or no effect on any of these activities.

Amino Acid Sequence↗