Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Receptors, Complement”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1988

Identification of an alternative polyadenylation site in the human C3b/C4b receptor (complement receptor type 1) transcriptional unit and prediction of a secreted form of complement receptor type 1.

The human C3b/C4b receptor or complement receptor type one (CR1) is an approximately 200-kD single chain membrane glycoprotein of human peripheral blood cells that mediates the binding, processing, and transport of C3b-bearing immune complexes and regulates the activity of the complement cascade. Analysis of partial cDNA clones has shown that the COOH terminus is composed predominantly of three tandemly repeated regions of 450 amino acids each (15). In this report, we present a cDNA sequence that encodes the NH2 terminus of CR1. It appears to have been derived from an alternatively processed transcript, caused by polyadenylation occurring at a site within an intron in the CR1 transcriptional unit. The resulting truncated messenger carries an open reading frame that would produce a short, secreted CR1 form. We present genomic sequences and Northern blots which support this hypothesis and we propose that the NH2-terminal end of CR1 is a likely location for active sites. In addition, we report evidence for a CR1-like sequence in the human genome and we present a model for the organization of CR1.

Amino Acid Sequence↗
PubMed1985

Migration and differentiation of bone marrow lymphocytes: development of surface immunoglobulin, Fc receptor, complement receptor, and functional responsiveness as studied with anti-allotype serum.

Immunofluorescent studies using fluorescein isothiocyanate-conjugated mouse anti-allotype antibody were carried out to study the migration pattern and the development of surface Ig (SIg), Fc receptor for IgG (FcR gamma), and complement receptor (CR) or mouse bone marrow lymphocytes following intravenous injection into congenic mice. After transfer of bone marrow cells from CSW mice into untreated congenic CWB mice, the absolute number of donor-type SIg-bearing (SIg+) cells and the proportion of either FcR gamma- or CR-bearing (FcR gamma+ or CR+) cells in donor-type SIg+ cells were evaluated in the recipient spleen and the results were compared with those obtained after the transfer of CSW spleen cells. After injection of donor bone marrow cells, detectable donor-type SIg+ cells, although few initially, increased from day 1 to Day 2 and reached a plateau thereafter. The proportion of FcR gamma+ cells in donor-type SIg+ cells, although very low in the donor marrow inoculum, increased progressively after 1 day to reach a maximum at Day 5 (90%). On the other hand, following the transfer of spleen cells, the proportion of FcR gamma+ cells remained at high levels (90%) for 5 days after transfer. Likewise, the proportion of CR+ cells in donor-type SIg+ cells was very low (less than 1%) in the original donor bone marrow cells but high (60%) in the donor spleen cells. However, in transferring bone marrow cells this proportion also increased in the recipient spleen to reach a maximum (49%) at Day 5 although it was lower compared to the percentage of FcR gamma+ cells in donor SIg+ cells. Furthermore, the ability of functional responsiveness to antigen was also examined in the same system by detecting plaque-forming cells (PFC) from donor origin. In transferring donor bone marrow cells into recipient, the participation of donor cells in the PFC response was very low when the recipients were primed with sheep red blood cells at Day 3 after transfer. However, when the recipients were primed at Days 7 to 21 after transfer, increasing numbers of the donor marrow-derived cells were involved in the PFC response. Thus, the present study demonstrates that the bone marrow-derived lymphocytes, albeit lacking both distinctive surface receptors (IgM, FcR gamma, CR) and the functional responsiveness to antigen, continue their development along the B-cell lineage after migrating into the spleen, as evidenced by the surface receptor expression and participation in the antibody response.

Animals↗
PubMed1987

Molecular cloning of the cDNA encoding the Epstein-Barr virus/C3d receptor (complement receptor type 2) of human B lymphocytes.

Complementary DNA clones for complement receptor type 2 (CR2), the B-lymphocyte membrane protein that serves as the receptor for Epstein-Barr virus and the C3d complement fragment, were obtained by screening a lambda gt11 library generated from Raji B lymphoblastoid cell mRNA. A 4.2-kilobase (kb) clone, representing the entire coding sequence of the protein plus untranslated 5' and 3' nucleotide sequences was obtained and sequenced. The 4.2-kb clone, which contains all but about 500 base pairs (bp) of the 5' untranslated region of the full-length CR2 mRNA, consists of 63 bp of 5' untranslated nucleotide sequence followed successively by a start codon, a 20-amino acid hydrophobic signal peptide, 1005 amino acids having a repeating motif, a 28-amino acid probable transmembrane domain, and a 34-amino acid cytoplasmic tail. The deduced amino acid sequence of the protein indicates that the extracellular domain consists entirely of 16 tandemly arranged repeating elements, each 60-75 amino acids in length, which are identified by multiple conserved residues. This repeating motif also occurs in the C3b/C4b receptor, several complement proteins, and a number of noncomplement proteins. In CR2, the 16 repeats occur in four clusters of four repeats each. Approximately 10% of the deduced amino acid sequence, including the amino and carboxyl termini, was confirmed by amino acid sequencing of tryptic peptides derived from purified CR2. The nucleotide and derived amino acid sequence of CR2 and related studies are presented here.

Amino Acid Sequence↗
PubMed1987

C3bi receptor (complement receptor type 3) recognizes a region of complement protein C3 containing the sequence Arg-Gly-Asp.

Human phagocytes express a receptor termed complement receptor type 3 (CR3) that recognizes the complement protein fragment C3bi. We show here that CR3 recognizes a region of C3 that contains the sequence Arg-Gly-Asp (RGD). CR3 is down-modulated upon spreading of macrophages on surfaces coated with a synthetic 21-residue peptide from C3 (residues 1383-1403). This peptide was also attached to erythrocytes by coupling myristic acid to its amino terminus and allowing the myristoylated peptide to bind to erythrocytes through hydrophobic interactions. Erythrocytes coated with this RGD-containing segment of C3 were bound by macrophages, and binding could be blocked by specific monoclonal antibodies against CR3. Since CR3 recognizes a peptide sequence that contains the RGD triplet, it appears to be a member of a larger family of adhesion-promoting receptors that recognize RGD-containing proteins. However, since CR3 does not recognize a hexapeptide containing RGD, we presume that residues beyond the RGD triplet contribute to binding. We have compared the RGD-containing region of fibronectin and vitronectin, proteins known to be recognized by means of their RGD-containing regions, with those in human and murine C3. A striking homology is observed over an approximately equal to 50 amino acid sequence present in all four proteins. We suggest that this extended region of homology contains a structure recognized by adhesion-promoting receptors.

Amino Acid Sequence↗
PubMed1988

Interaction of human monomeric C3b with its receptor (complement receptor type 1, CR1) on neutrophils. Evidence for negative cooperativity.

The binding of highly purified monomeric 125I-C3b to its receptor (CR1) on resting human polymorphonuclear neutrophils (PMN) was analyzed under equilibrium conditions, at 4 degrees C and low ionic strength. Scatchard analysis of specific binding data yielded curvilinear concave upward plots, which resulted from the presence of site-site interactions of the negative type among PMN C3b-receptors (negative cooperativity), as shown by dissociation kinetic experiments. Indeed, the dissociation rate of 125I-C3b from PMN was markedly increased in the presence of an excess of unlabeled C3b in the dilution medium and was directly dependent on the degree of initial receptor occupancy with the radioligand. These interactions occurred when 2% of the receptors were occupied with 125I-C3b and resulted in a 4-fold decrease in CR1 affinity when the receptor went from its "empty" to its "filled" conformation. In a disease associated with a continuous production of C3b (factor I deficiency), CR1 on in vivo circulating PMN was found to be in a "low affinity" and "high dissociating" state similar to that of normal CR1 at high occupancy. Finally, negative cooperativity among CR1 sites disappeared after PMN activation with chemotactic peptides.

Afibrinogenemia↗
PubMed1977

Ontogeny of the antibody-forming cell line in mice. IV. Appearance of cells bearing Fc receptors, complement receptors, and surface immunoglobulin.

The ontogeny of Ig, FcR, and CR-bearing cells in liver and spleen has been followed by using rosetting procedures. These studies demonstrated a sequential appearance of surface receptors during development. Two types of Ig+ cells could be distinguished according to their rosette morphology and adherence to carbonyl iron: 1) an adherent cell which bound few erythrocytes was found predominantly in fetal liver from 13 days gestation and 2) a nonadherent cell which bound larger numbers of erythrocytes appeared in small numbers in fetal liver from day-16 gestation but represented the major Ig+ cell type after birth. Changes in the proportions of receptor-bearing populations occurred at two particular periods during ontogeny. The first was at birth, where an increase in the proportion of FcR+ cells occurred and the proportion of type 2 Ig+ cells rose rapidly. This probably represented the first appearance of FcR+ B lymphocytes even though cells bearing FcR were detected in fetal liver of all ages (days 12 to 18). The second period was around 10 days after birth when the proportion of Ig+ cells again increased concomitant with the appearance of CR+ nonadherent cells.

Aging↗
PubMed1994

Molecular characterization of rat glomerular epithelial cell complement receptors.

Complement receptor type 1 (CR1) has previously been isolated from cultured rat glomerular epithelial cells (GEC) by C3b affinity chromatography. In addition, the presence of Crry in GEC and in rat glomeruli has been demonstrated. Crry appears to be the rodent analogue of human decay accelerating factor, which was previously described in human GEC and in human glomeruli. In this study, the molecular biology of these rat complement receptors is examined. A specific cDNA probe for rat CR1 was generated by reverse transcription of GEC mRNA, followed by polymerase chain reaction (PCR). The oligonucleotide primers were chosen from conserved regions spanning 271 bases in human and mouse CR1. A 271-base-pair PCR product was generated from rat GEC cDNA, the nucleotide sequence of which was 70.1% and 77.2% identical to those of the respective mouse and human sequences. This PCR product, designated rCR1-p, was then used to probe for CR1 mRNA. By northern blot analysis, rCR1-p hybridized to 4.5-kilobase (kb) mRNA from both cultured GEC and rat glomeruli and also weakly hybridized to 4.5-kb CR1 mRNA from mouse spleen. In additional northern blots, a nucleotide probe for mouse Crry hybridized to mRNA of 2.1 to 2.4 kb from rat GEC, slightly larger than the 1.9- to 2.1-kb mouse Crry mRNA. Therefore, mRNA for CR1 and Crry are present in cultured rat GEC and in rat glomeruli in vivo. To further investigate the composition of rat CR1 mRNA, northern hybridizations were performed with nucleotide probes for mouse and human CR1.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed2004

Differential expression of the C5a receptor and complement receptors 1 and 3 after LPS stimulation of neutrophils and monocytes.

Animal experiments recently suggested that administration of anti-C5a, anti-C5a receptor or soluble complement receptor type-1 may be of value in the treatment of septic shock. Because results regarding C5a receptor expression (C5a-R, CD-88) have been found to differ between septic animals and patients, the aim of this study was to investigate the neutrophil and monocyte receptor expression of CD-88 and complement receptor-1 (CR-1, CD-35) after stimulation with lipopolysaccharide (LPS) ex vivo. Whole blood or isolated neutrophils and monocytes from healthy people were incubated with LPS in a dose range of 0.1-1000 ng/ml. The expressions of CD-88 and CD-35 were analysed by means of flow cytometry. For comparison, the expressions of complement receptor-3 (CR-3, CD-11b/CD-18), Fc-gamma receptor type-I (CD-64) and CEACAM-8 (CD-66b) were also investigated. In whole blood, CD-88 expression on neutrophils was reduced (P < 0.05). The expressions of CD-35 and CD-11b were increased both on neutrophils (P < 0.001; P < 0.05) and on monocytes (P < 0.001; P < 0.001). No effect was observed on isolated cells. In agreement with the findings in septic patients, LPS reduced the neutrophil C5a-R expression, whereas the expressions of CR-1 and CR-3 were increased. The effects of LPS were indirect and were mediated via factors in the blood. The clinical significance of this is not known, but may be associated with decreased chemotaxis.

Adult↗
PubMed1986

Loss of complement receptor type 1 (CR1) on ageing of erythrocytes. Studies of proteolytic release of the receptor.

Complement receptor type 1 (CR1) is a glycoprotein of Mr about 250 000 present on erythrocytes and other cell types. CR1 acts as a cofactor in the factor I-mediated breakdown of complement fragment C3b to form iC3b. Using an assay of cofactor activity, a wide variation in mean CR1 levels between erythrocytes from individual donors is observed. CR1 levels also decrease on ageing of erythrocytes in vivo, and again the rate of loss is widely variable between individuals. However, variable loss of CR1 during ageing of erythrocytes is likely to make only a minor contribution to the observed variation in mean CR1 levels. CR1 is very sensitive to proteolysis, and random proteolytic removal of CR1 from erythrocytes is likely to be an important factor in loss of CR1 on ageing of red cells in vivo. In vitro, mild trypsin treatment, plasmin or thrombin digestion of erythrocytes results in the loss of the factor I cofactor activity from the cell surface, and appearance of this activity in the supernatant. We conclude that an active fragment of CR1 is released from the cell surface on proteolysis. Subsequent prolonged trypsin treatment destroys most of the activity of this fragment. Proteolytic removal of CR1 from red cells may account not only for loss on ageing of cells, but also for the acquired CR1 deficiencies observed by others in systemic lupus erythematosus.

Erythrocyte Aging↗
PubMed1992

The up- and down-modulation of immunoglobulin G Fc receptors and complement receptors on activated human neutrophils depends on the nature of activator.

Human neutrophils were activated with soluble stimuli, formyl-methionyl-leucyl-phenylalanine (fMLP) or ionophore A23187, and with opsonized particles, zymosan or Streptococcus pneumoniae bacteria. Monoclonal antibodies and flow cytometry were used to assess the expression of Fc-gamma receptors (FcRI, FcRII, FcRIII) and complement receptors (CR1, CR3). The role of extracellular calcium and magnesium in the modulation of receptor expression was also examined. The low-level expression of FcRI was not affected by any activator tested. fMLP and A23187 did not alter the expression of FcRII, whereas a significant, Ca(2+)- and Mg(2+)-independent down-modulation was observed upon activation with opsonized particles. All activators clearly decreased the surface expression of FcRIII in the presence of Ca2+ and Mg2+, probably as a consequence of shedding of the phosphatidylinositol-glycan-anchored receptor protein. The removal of calcium and magnesium blocked the shedding of FcRIII caused by soluble stimuli, whereas it retarded but did not abolish the fall in FcRIII expression when cells were incubated with opsonized particles. This fall was likely due to internalization of the receptor molecules while the shedding was blocked. A rapid increase in CR1 and CR3 expression was seen upon activation with soluble stimuli. The change in CR1 expression was independent of extracellular Ca2+ and Mg2+. The increase in CR3 number required an influx of divalent cations. No total up-modulation of complement receptors occurred when neutrophils were activated with opsonized particles. However, the kinetic analysis revealed a temporary up-modulation that was followed by a down-modulation. The results indicate that the expression of both Fc-gamma and complement receptors on human neutrophils is changed upon activation and that the up- and down-modulation of these receptors depends on the nature of activator. We also suggest that in neutrophils the FcRIII down-modulation is the result of both receptor shedding and internalization, while FcRII is down-modulated by receptor internalization.

Calcimycin↗
PubMed1991

Adherence of neutrophils to hemodialysis membranes: role of complement receptors.

Complement activation occurs during hemodialysis using cellulosic dialysis membranes with the consequent deposition of C3 activation and degradation products on the membrane surface. To determine if these complement fragments are functionally active, we examined their capacity to mediate leukocyte adherence to cuprophan membranes. Immunoblotting of proteins eluted from plasma-treated cuprophan membranes confirmed the presence of both C3b and iC3b. Incubation of cuprophan membranes with heparinized whole blood resulted in adherence of leukocytes but not erythrocytes. Neutrophils were the primary cell type bound, with monocytes comprising less than 5% of the adherent cells. Studies using indium-labeled neutrophils demonstrated that the binding was plasma dependent and increased with time up to two hours. Neutrophil binding was inhibited by preincubation of the plasma-treated cuprophan membrane with anti-C3 or preincubation of neutrophils with an antibody directed against the alpha chain of complement receptor type 3 (CR3). These observations indicate that iC3b deposited on cuprophan membrane surface as a result of complement activation mediates neutrophil adherence via interaction with CR3. They also support the hypothesis that, in addition to the anaphylatoxins released into the fluid phase, complement activation products that remained membrane bound during hemodialysis also stimulate pathophysiological responses.

Cell Adhesion↗
PubMed1985

The role of complement receptor positive and complement receptor negative B cells in the primary and secondary immune response to thymus independent type 2 and thymus dependent antigens.

Both complement receptor positive (CR+) and complement receptor negative (CR-) B cells have been shown to be involved in the primary immune response to PC-Hy (phosphocholine conjugated hemocyanin), a thymus dependent (TD) antigen which preferentially induces antibody secretion in Lyb-5+ B cells during a primary adoptive transfer assay. CR+ and CR- B cells also responded in a primary adoptive transfer assay to TNP-Ficoll, a thymus independent type 2 (TI-2) antigen which activates only Lyb-5+ B cells. When the secondary immune response to PC-Hy and TNP-Ficoll were analyzed, it was found that most of the immune memory to both antigens was present in the CR- B cell subset. The CR- B cell subset also dominated the secondary immune response to PC-Hy in immune defective (CBA/N X DBA/2N)F1 male mice. These data indicate that CR- B cells dominate the memory response in both the Lyb-5+ and Lyb-5- B cell subsets of normal and xid immune defective mice and suggest that Lyb-5+ and Lyb-5- B cells can be subdivided into CR+ and CR- subsets.

Animals↗
PubMed2005

Neutrophils interact with adenovirus vectors via Fc receptors and complement receptor 1.

Neutrophils are effectors of the innate immune response to adenovirus vectors. Following the systemic administration of Cy2-labeled AdLuc in mice, flow cytometry and PCR analysis of liver leukocytes revealed that 25% of recruited neutrophils interacted with adenovirus vectors. In vitro, flow cytometry of human neutrophils incubated with Cy2-labeled AdLuc also demonstrated a significant interaction with adenovirus vectors. Fluorescence and electron microscopy confirmed vector internalization by neutrophils. The AdLuc-neutrophil interaction reduced vector transduction efficiency by more than 50% in coincubation assays in epithelium-derived cells. Adenovirus vector uptake by neutrophils occurred independently of coxsackievirus adenovirus receptor (CAR) and capsid RGD motifs, since neutrophils do not express CAR and uptake of the RGD-deleted vector AdL.PB* was similar to that of AdLuc. Furthermore, both AdLuc and AdL.PB* activated neutrophils and induced similar degrees of L-selectin shedding. Neutrophil uptake of AdLuc was dependent on the presence of complement and antibodies, since the interaction between AdLuc and neutrophils was significantly reduced when they were incubated in immunoglobulin G-depleted or heat-inactivated human serum. Blocking of complement receptor 1 (CD35) but not complement receptor 3 (CD11b/CD18) significantly reduced neutrophil uptake of AdLuc. Blocking of Fc gammaRI (CD64), Fc gammaRII (CD32), and Fc gammaRIII (CD16) individually or together also reduced neutrophil uptake of AdLuc, although less than blocking of CD35 alone. Combined CR1 and Fc receptor blockade synergistically inhibited neutrophil-AdLuc interactions close to baseline. These results demonstrate opsonin-dependent adenovirus vector interactions with neutrophils and their corresponding receptors.

Adenoviridae↗
PubMed1994

Increased respiratory burst activity is associated with normal expression of IgG-Fc-receptors and complement receptors in peripheral neutrophils from patients with juvenile periodontitis.

The respiratory burst activity in peripheral neutrophils from nine patients with localized juvenile periodontitis (LJP) and age- and sex-matched healthy controls was studied by measuring the intensity of luminol-enhanced chemiluminescence (CL) induced by unopsonized and three differently opsonized zymosan particles, formyl-methionyl-leucyl-phenylalanine (FMLP) or phorbol myristate acetate (PMA). The neutrophils from LJP patients showed in general more intense CL with all activators than did their controls. Particularly, the CL response induced by unopsonized zymosan particles and FMLP were significantly higher (p < 0.05 and 0.001). When comparisons were made between female LJP patients (n = 6) and matched controls, also serum-opsonized and IgG-opsonized zymosan particles produced CL was significantly increased (p < 0.05). In order to determine whether the elevated CL responses to zymosan particles were due to altered levels of the interacting receptors on neutrophil surface, an immunofluorescence analysis of the expression of IgG-Fc-receptors (FcR) and complement receptors (CR) was performed with flow cytometry. No significant difference in the expression of FcRII, FcRIII, CR1 and CR3 was detected in LJP group compared to controls. Since the elevated CL responses can not be explained by changes in receptor numbers it is hypothesized that the increased respiratory burst activity in LJP may be caused by altered post receptor signalling pathway.

Adolescent↗
PubMed1991

Flow cytometric assay for phagocytosis of human monocytes mediated via Fc gamma-receptors and complement receptor CR1 (CD35).

We developed a simple flow cytometric assay for phagocytosis by human monocytes that is mediated via Fc gamma receptors and the complement receptor CR1 (CD35), using fluorescent latex beads carrying IgG and complement components C4b and C3b. To prepare fluorescent latex beads carrying IgG(BA), BSA-coated latex beads (B) were incubated with diluted rabbit anti-BSA IgG. To bind complement components, BA-particles were incubated with whole human serum pretreated with K-76 monocarboxylic acid (K-76COOH). K-76COOH inhibits the activities of C5 and factor I (12,13), resulting in the deposition of C1,4b,2a,3b on BA-particles (BAC1,4b,2a,3b). Further incubation of BAC1,4b,2a,3b with EDTA-GVB at 37 degrees C gave particles carrying IgG and C4b,C3b (BAC4b,3b). The C3 fragment, C3b, was confirmed to present on BAC1,4a,2a,3b particles by SDS-PAGE and immunoblot, and these particles were calculated to have approximately 25,000-30,000 C3b molecules per particle. To evaluate the particle attachment, the phagocytic assay was performed with 3 microM cytochalasin D treated cells. The percent cells with ingested particles and the number of ingested particles/100 cells for 60 min were estimated, being 5.1% and 5.4 for B, 12.3% and 26.7 for BA, 42.5% and 108.7 for BAC4b,3b, and 42.6% and 112.5 for BAC1,4b,2a,3b, respectively.

Antigens, Differentiation↗
PubMed1997

Febrile infection changes the expression of IgG Fc receptors and complement receptors in human neutrophils in vivo.

We have examined the expression of the IgG Fc receptors (FcRI, FcRII, FcRIII) and complement receptors (CR1, CR3) in neutrophils from 42 patients with febrile bacterial infection, 20 patients with febrile viral infection and 69 non-febrile healthy individuals. Using receptor-specific MoAbs and immunofluorescence flow cytometry the relative fluorescence intensity (as a measure of receptor number) and the proportion of receptor-positive cells were determined in peripheral blood neutrophils exposed to minimal processing, consisting only of erythrolysis. Both the percentage of FcRI-positive neutrophils and FcRI number per neutrophil were significantly (P < 0.001 and P < 0.0001) increased in bacterial infected patients compared with controls, whereas in viral infected patients only the FcRI percentage was markedly elevated (P < 0.05). In addition, both FcRII and CR1 levels were significantly higher in the bacterial infection group than in the viral infection and control groups (bacterial versus control P < 0.001, bacterial versus viral P < 0.0001). No changes in expression of FcRIII or CR3 were found in the patient groups. The kinetic analysis of receptor expression in bacterial infection patients revealed a shift in the percentage of FcRI-bearing neutrophils towards normal values already on day 2 after the first analysis. On the other hand, the levels of FcRI, FcRII and CR1 remained clearly elevated in these patients during 1 week's follow-up period. We conclude that febrile infection may cause systemic activation of the entire pool of circulating neutrophils, resulting in alterations in cell surface receptor expression, some of which are characteristic of the nature of the infectious agent.

Adolescent↗