PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Receptors, Complement 3d”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 397 records · Page 22Linked to original sources
PubMed2004

Murine hindlimb reperfusion injury can be initiated by a self-reactive monoclonal IgM.

BACKGROUND: Murine hindlimb reperfusion injury (I/R), is initiated by activation of the classical pathway of complement. Complement receptor-2 knockout mice (Cr2-/-) are protected from I/R injury due to defective B-1 cells with a resulting deficient natural immunoglobulin M (IgM) repertoire. Cr2-/- and wild type (WT) mice were studied to isolate the antibody or antibodies responsible for initiation of I/R. METHODS: IgM-secreting B-1 cell clones were produced with hybridoma technology from WT cells. Of 21 clones tested in murine I/R models, only 1 clone, CM22, was found to restore injury in protected mice. Cr2-/- mice reconstituted with IgM from individual clones, WT serum, or saline were subjected to 2 hours hindlimb ischemia and 3 hours reperfusion and compared with WT. RESULTS: Muscle injury in Cr2-/- mice reconstituted with CM22 was similar to injury in WT mice reconstituted with saline and Cr2-/- mice reconstituted with WT serum. This injury was 137% greater (P < .05) than in both Cr2-/- mice reconstituted with saline and those reconstituted with a different IgM clone, CM31. IgM and C3 deposition was found only on injured muscle of WT mice or Cr2-/- mice reconstituted with CM22 or WT serum. CONCLUSION: A single clone of self-reactive IgM, CM22, can initiate complement-dependent I/R injury.

Animals↗
PubMedDate not supplied

Expression of CR1/2 receptor on alloantigen-stimulated mouse T cells.

Antibodies can mediate injury of organ transplants by several mechanisms, including complement activation and interaction with Fc receptors on cells. We tested the hypothesis that antibodies could also cause up-regulation of complement receptors on cells to increase the responses to complement activation by interaction with split products of C3. In our experimental model, B10.A (H-2(a)) cardiac transplants survive significantly longer in C57BL/6 (H-2(b)) immunoglobulin knockout recipients (IgKO) than in their wild-type counterparts. Passive transfer of specific antibodies to donor MHC class I to IgKO recipients of cardiac allografts at the time coinciding with a vigorous cellular infiltration reconstituted acute rejection. We tested the effects of alloantibodies on CR1/2 expression by alloantigen-stimulated T cells. Both CD4(+)/CR1/2(+) and CD8(+)/CR1/2(+) populations of T cells were expanded in C57BL/6 splenocytes stimulated by B10.A alloantigen in 7-day MLR after coculture with endothelial cells sensitized with IgG1 and IgG2b mAb specific to MHC. Endothelial cells sensitized with antibodies also caused an expansion of CD8(+) T cells expressing CR1/2 in lymph node lymphocytes harvested from a C57BL/6 recipient of a B10.A cardiac allograft. These data suggest that antibodies can augment the cellular rejection process through expanding the population of T cells interacting with complement split products.

Animals↗
PubMed2004

Independent but not synergistic enhancement to the immunogenicity of DNA vaccine expressing HIV-1 gp120 glycoprotein by codon optimization and C3d fusion in a mouse model.

The ability to elicit humoral and cell-mediated immune (CMI) responses from DNA immunization by combinational use of codon optimization and C3d component of complement was evaluated in this study. DNA vaccines that express either the wild type or the codon optimized gp120 gene coding for the envelope (Env) glycoprotein of human immunodeficiency virus (HIV-1) from the primary isolate JR-FL strain were compared to the same forms fused to three tandem copies of the murine C3d genes. Either codon optimization or C3d fusion alone was effective at generating early appearance, higher binding and neutralizing antibody responses. We also observed that cell-mediated immune responses against HIV Env could also be enhanced by C3d fusion. However, for both humoral and CMI responses, there were no synergistic effects when the combination of codon optimization and C3d fusion was employed.

AIDS Vaccines↗
PubMed2004

Effective immunotherapy against canine visceral leishmaniasis with the FML-vaccine.

The potential effect of the fucose mannose ligand (FML)-vaccine on immunotherapy of canine visceral leishmaniasis was assayed on five mongrel dogs experimentally infected with Leishmania donovani and on 21 Leishmania chagasi naturally infected dogs when seropositive to FML but completely asymptomatic. The clinical signs of the experimentally infected, symptomatic dogs only disappeared after the complete vaccination. Protection was obtained in 3/5 animals that remained asymptomatic, IDR positive and parasite free, 1 year after infection. Furthermore, the asymptomatic, FML-vaccine treated dogs showed stable anti-FML IgG1 levels, increasing IgG2 levels and 79-95% of positive DTH response, during the whole experiment. Twenty-two months after complete vaccination, no obits due to visceral leishmaniasis were recorded and 90% of these dogs were still asymptomatic, healthy and parasite free. On the other hand, 37% (17/46 dogs) kala-azar obits were recorded in a control group that received no treatment during the same period, and that was FML-seropositive and asymtpomatic at the beginning of the assay. Our results indicate that the FML-vaccine was effective in the immunotherapy against visceral leishmaniasis of asymptomatic infected dogs. Normal proportions of CD4 and CD21 lymphocytes were detected in PBMC by FACS analysis, in dogs submitted to immunotherapy, suggesting their non-infectious condition. All animals showed as well significantly increased percents of CD8 lymphocytes as expected for Quillaja saponin (QuilA) vaccine treatments.

Adjuvants, Immunologic↗
PubMed2004

DNA immunization with plasmids expressing hCGbeta-chimeras.

Human chorionic gonadotropin has been used as an anti-fertility vaccine and as a target for cancer immunotherapy. We have explored the use of DNA immunization with the aim of improving the immunogenicity of this hormone. Stimulating the muscle with electric pulses following intramuscular injection of plasmids expressing hCGbeta resulted in higher levels of human chorionic gonadotropin (hCG)-specific antibodies, which could be further enhanced following a protein boost with hCG mixed with adjuvant. DNA vaccines encoding a membrane attached or a secreted form of hCGbeta produced similar-albeit relatively modest-antibody responses. Providing hCGbeta with additional T cell help by vaccinating with a plasmid encoding a hCGbeta-hFc fusion protein did not further increase the antibody levels in the immunized animals. However, immunization of mice with a construct encoding hCGbeta fused to C3d(3) produced significantly lower antibody levels relative to mice immunized with the hCGbeta-alone expression plasmid, even though the hCGbeta-C3d(3) chimera was expected to facilitate cross-linking of the antigen-specific B-cell receptor and CR2 thereby lowering the threshold of activation. Thus the limiting factor determining the antibody levels following hCGbeta immunization, at least for DNA immunization, is related to the amount of protein available rather than the form of protein produced or lack of T cell epitopes.

Adjuvants, Immunologic↗
PubMed2005

Immunization with a DNA chimeric molecule encoding a hemagglutinin peptide and a scFv CD21-specific antibody fragment induces long-lasting IgM and CTL responses to influenza virus.

Killed viral vaccines are known to induce primarily antibody responses. By contrast DNA vaccination using naked DNA encoding viral antigens induces both humoral and cellular immune responses. Various approaches have been used to construct DNA vaccines with build-in adjuvanticity. We hypothesized that sequences encoding a common epitope of influenza A virus hemagglutinin jointed to sequences encoding a single-chain variable fragment (scFv) antibody fragment to a costimulatory B cell surface receptor would result in the in vivo expression of a chimeric viral peptide with increased immunogenicity. Such a hybrid DNA molecule was constructed by us, encoding a T and B cell epitope-containing influenza hemagglutinin peptide and a scFv antibody fragment binding to mouse complement receptors I and II (CR1 and CR2). A single immunization with a plasmid containing the described construct induced a strong anti-influenza cytotoxic response lasting for more than six months and a weak antibody response.

Adjuvants, Immunologic↗
PubMed2006

T cell-independent and T cell-dependent immunoglobulin G responses to polyomavirus infection are impaired in complement receptor 2-deficient mice.

Polyomavirus (PyV) infection induces protective T cell-independent (TI) IgM and IgG antibody responses in T cell-deficient mice, but these responses are not generated by immunization with viral proteins or virus like particles. We hypothesized that innate signals contribute to the generation of isotype-switched antiviral antibody responses. We studied the role of complement receptor (CR2) engagement in TI and T cell-dependent (TD) antibody responses to PyV using CR2-deficient mice. Antiviral IgG responses were reduced by 80-40% in CR2-/- mice compared to wild type. Adoptive transfer experiments demonstrated the need for CR2 not only in TD, but also in TI IgG responses to PyV. Transfer of CR2-/- B lymphocytes to SCID mice resulted in TI antiviral IgG responses that corresponded to 10% of that seen in wild-type B cell-reconstituted mice. Thus, our studies revealed a profound dependence of TI and TD antiviral antibody responses on CR2-mediated signals in PyV-infected mice, where the viral antigen is abundant and persistent.

Adoptive Transfer↗
PubMed2006

Improved gene delivery to B lymphocytes using a modified adenovirus vector targeting CD21.

Gene transfer by adenoviruses, which are widely used for gene therapy, may provide an alternative approach to treatment of several hematopoietic malignancies. However, a major limitation of adenovirus 5-based gene therapy lies in the natural tropism of the virus for the widely expressed hCAR receptor. The efficacy of adenoviral vectors could be improved if viral vectors that exhibit tissue-specific gene delivery were developed. For efficient gene transfer it is essential that every step from binding of virus to target cells to transgene expression is successfully accomplished. We developed a specific vector targeting the CD21 receptor, by inserting a CD21 binding sequence, derived from the EBV GP350/220 protein, into the HI loop of the HAdV5 fiber protein. This vector, HAdV5-CD21HIloop, binds specifically to CD21-positive cells and results in enhanced expression of the transgene in these cells and reduced expression in CD21-negative cells. Viral infection is highly correlated with the presence of CD21 receptors. Taken together, these results demonstrate that HAdV5-CD21HIloop is able to transduce CD21-positive cells specifically with reduced infection of nontarget cells. This is the result of the maintenance of the intracellular trafficking of the genetically modified adenovirus without vesicular retention, leading to enhanced nuclear transfer.

Adenoviridae↗
PubMed1994

Hormonal regulation of complement components and receptors throughout the menstrual cycle.

OBJECTIVES: Complement components have been recently demonstrated to be present in the reproductive tract. Among these components, C3 synthesis by glandular epithelium of the rat uterus has been shown to be regulated by estrogen; progesterone inhibits this synthesis. However, the hormonal regulation of C3 and the presence of other complement factors in the human has not been investigated to date. In this study we examined the presence and the hormonal regulation of different complement components and receptors in the human endometrium at various phases of the menstrual cycle of normally cycling women with no pelvic pathologic abnormalities. STUDY DESIGN: Endometrial tissue was obtained from normally cycling women, and immunohistochemistry was performed by means of monoclonal antibodies against C3, factors B, decay-accelerating factor, membrane cofactor protein, and complement receptor types 1, 2, and 3. The tissue was incubated with minimal essential media without methionine containing methionine labeled with sulfur 35. Immunoprecipitations were performed on the media with goat antihuman C3 antibody, and the proteins were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. RESULTS: C3 was found to be present in the glandular epithelial cells of luteal endometrium. Biosynthesis as analyzed by immunoprecipitation with anti-C3 antibody was found to increase during the luteal phase of the cycle and to be minimal in the proliferative phase. Like C3, factor B and decay-accelerating factor were localized to the luteal glandular epithelial cells. In contrast, membrane cofactor protein was found to be present in the glandular epithelium throughout the menstrual cycle, and complement receptor type 1 was present only in the stromal compartment of luteal endometrium. Complement receptor type 3 was present only in the infiltrating leukocytes in the luteal endometrium, whereas complement receptor type 2 was undetectable. CONCLUSIONS: These findings suggest that several components of the complement system exist in the human endometrium in a hormone-dependent manner and may play a role in normal reproductive function.

Adult↗
PubMed2001

Immunological characterization of human vaginal xenografts in immunocompromised mice: development of a small animal model for the study of human immunodeficiency virus-1 infection.

A small animal model for the in vivo study of human immunodeficiency virus-1 and other fastidious infectious agents in human host target tissues is critical for the advancement of therapeutic and preventative strategies. Our laboratory has developed a human vaginal xenograft model that histologically recapitulates features of the human vaginal epithelial barrier. Vaginal xenografts were surgically implanted into C.B.-Igh-1(b)/IcrTac-Prkdc(scid) (SCID) and NOD/LtSz-scid/scid (NOD/SCID) mice, with and without human peripheral blood mononuclear cell reconstitution. Immunohistochemical staining of vaginal xenografts demonstrated that in the SCID strain healed vaginal xenografts did not retain intrinsic human immune cells at baseline levels, whereas the NOD/SCID strain supported retention of intrinsic human immune cell populations within the xenografts for at least 2 months after engraftment. In peripheral blood mononuclear cell-reconstituted NOD/SCID mice with vaginal xenografts, flow cytometric analyses detected human immune cell populations in the peripheral blood and immunohistochemical methods detected infiltration of human CD45+ cells in the mouse spleens and vaginal xenografts for at least 2 months after reconstitution. This optimized NOD/SCID human vaginal xenograft model may provide a unique small animal in vivo system for the study of human immunodeficiency virus-1 transmission and infection.

Animals↗
PubMed2003

CD21-positive follicular dendritic cells: A possible source of PrPSc in lymph node macrophages of scrapie-infected sheep.

Natural sheep scrapie is a prion disease characterized by the accumulation of PrP(Sc) in brain and lymphoid tissues. Previous studies suggested that lymph node macrophages and follicular dendritic cells (FDC) accumulate PrP(Sc). In this study, lymph nodes were analyzed for the presence of PrP(Sc) and macrophage or FDC markers using dual immunohistochemistry. A monoclonal antibody (mAb) to the C-terminus of PrP reacted with CD172a+ macrophages and CD21+ FDC processes in secondary follicles. However, a PrP N-terminus-specific mAb reacted with CD21+ FDC processes but not CD172a+ macrophages in secondary follicles. Neither the PrP N-terminus nor C-terminus-specific mAb reacted with CD172a+ macrophages in the medulla. These results indicate that lymph node follicular macrophages acquire PrP(Sc) by phagocytosis of CD21+ FDC processes. The results also suggest that follicular macrophages have proteases that process full-length PrP(Sc) to N-terminally truncated PrP(Sc).

Animals↗
PubMed2001

Down-regulation of human B lymphocyte activities by a Trypanosoma cruzi membrane glycoprotein.

The effects of purified AGC10, a Trypanosoma cruzi membrane glycoprotein, on normal human B lymphocytes were studied in this work. In the presence of AGC10, [3H]-thymidine uptake by human peripheral blood mononuclear cells stimulated with the B cell-specific mitogen SACI (killed Staphylococcus aureus Cowan I) was markedly decreased. This alteration was accompanied by others such as decreased expression of the CD122 and CD132 chains of the IL-2R complex. These inhibitory effects appeared to be somewhat selective, as expression of CD25, another IL-2R chain, was not affected by AGC10 and no significant modification occurred in the expression of the B-cell-specific marker CD19 or CD21. In contrast, AGC10 did reduce the levels of expression of CD86 and CD80, molecules known to play critical roles in B cell interactions with T lymphocytes. Fairly large subpopulations of, but not all, B lymphocytes had their expression of CD122(+), CD132(+), CD86(+) and CD80(+) reduced to undetectable levels in the presence of AGC10. However, the SACI-activated B cells that remained capable of expressing these molecules in the presence of AGC10 did so at normal levels. This was denoted by comparable mean fluorescence intensity values representing the expression of CD122, CD132, CD86 or CD80 molecules on the surface of SACI-stimulated CD19(+) cells cultured without or with AGC10. These results indicated that AGC10, derived from an organism that causes immunosuppression in infected hosts, down-regulates B cell activities and suggested that the relevant mechanism could involve the molecular alterations described above.

Adolescent↗
PubMed2001

Generation of recombinant human C3dg tetramers for the analysis of CD21 binding and function.

CD21 (complement receptor 2, CR2) binds the terminal proteolytic fragments of the third component of complement (C3) that have been covalently attached to immune complexes or other targets during the activation of complement. We used the technique of in vivo biotinylation to create a recombinant multivalent ligand for CD21. A sequence coding for a biotinylation signal peptide was added to the 3' end of the human C3dg cDNA. The modified C3dg was expressed in Escherichia coli and biotinylated intracellularly by the bacterial biotin holoenzyme synthetase (BirA) enzyme. Monomeric C3dg was unable to bind to CD21 as determined by flow cytometry, while biotinylated recombinant C3dg (rC3dg) complexed with fluorochrome-conjugated streptavidin bound tightly. Binding was observed using CD21 positive B cells but not seen on pre-B cells that do not express this complement receptor. Two assays were used to assess the functional capacity of the recombinant C3dg. First, multimeric C3dg caused the phosphorylation of the mitogen-activated kinase, p38, in mature B lymphoma cells. Second, C3dg greatly enhanced the activation of primary B cells in combination with a sub-stimulatory concentration of anti-IgM monoclonal antibody. These results illustrate the utility of the technique of in vivo biotinylation to generate ligands for cell surface receptors that require multimerization for high avidity binding and function.

Amino Acid Sequence↗
PubMed2002

Purification and characterization of soluble CD21 from human plasma by affinity chromatography and density gradient centrifugation.

Complement receptor II (CD21) is the receptor for C3d fragments on immune complexes. It also serves as a receptor for Epstein-Barr virus (EBV) and on B-lymphocytes CD21 amplifies signalling through the B cell receptor. CD21 is shed from the surface of the cell and is found circulating in plasma. There, soluble CD21 (sCD21) binds to CD23 and complement fragments, thereby modulating the immune response. sCD21 activates monocytes through binding to membrane CD23. The clinical significance of sCD21 is shown by the increased levels found in the sera of patients with B lymphomas, EBV infections and other lymphoblastoid tumors. In this paper, we report the isolation of soluble CD21 from human plasma using affinity chromatography and density gradient centrifugation. sCD21 was found to be a single 126 kDa molecular species. By determining the sedimentation coefficient, we have calculated the partial specific volume, diffusion coefficient and frictional coefficient of the protein. These values show that the sCD21 isolated from human plasma is an elongated rod-shaped molecule.

Cell Line↗
PubMed2002

Retention of antigen on follicular dendritic cells and B lymphocytes through complement-mediated multivalent ligand-receptor interactions: theory and application to HIV treatment.

In HIV-infected patients, large quantities of HIV are associated with follicular dendritic cells (FDCs) in lymphoid tissue. During antiretroviral therapy, most of this virus disappears after six months of treatment, suggesting that FDC-associated virus has little influence on the eventual outcome of long-term therapy. However, a recent theoretical study using a stochastic model for the interaction of HIV with FDCs indicated that some virus may be retained on FDCs for years, where it can potentially reignite infection if treatment is interrupted. In that study, an approximate expression was used to estimate the time an individual virion remains on FDCs during therapy. Here, we determine the conditions under which this approximation is valid, and we develop expressions for the time a virion spends in any bound state and for the effect of rebinding on retention. We find that rebinding, which is influenced by diffusion, may play a major role in retention of HIV on FDCs. We also consider the possibility that HIV is retained on B cells during therapy, which like FDCs also interact with HIV. We find that virus associated with B cells is unlikely to persist during therapy.

Anti-HIV Agents↗
PubMed2000

The role of complement in B cell activation and tolerance.

It is becoming well accepted that innate immunity serves as a natural adjuvant in enhancing and directing the adaptive immune response. In this review, I have discussed how the complement system, a major mediator of innate immunity, links the two systems. The recent availability of knockout mice bearing selective deficiencies in the critical complement proteins and receptors has allowed formal demonstration of the importance of complement in enhancement of humoral immunity. Characterization of the mice has also uncovered mechanisms for maintaining survival of activated B cells within the lymphoid compartment. For example, co-ligation of the CD21/CD19/Tapa-1 receptor with the BCR not only reduces the threshold for B cell follicular survival but provides a unique signal for survival in the germinal centers. In addition complement receptors are critical for localization of antigen and C3d ligand to FDCs for maintenance of long-term B cell memory. A surprise that has come from analysis of the deficient mice is that complement is also important in negative selection of B lymphocytes. This observation provides new insight to a long-standing enigma that the major predisposing factor in lupus is deficiency in complement C1q or C4. The seeming contradiction of dual role for complement in both B cell activation and tolerance is reconciled by the hypothesis that natural IgM provides a mechanism to selectively identify self-antigens that are highly conserved and cross-react with microbial ones such as DNA and nuclear proteins. Thus, the importance of complement in tolerance to self-antigens is restricted to those self-antigens that are evolutionary conserved, and they are identified by natural antibody. The future should hold further surprises as to the intricate interactions between the complement system and acquired immunity.

Adjuvants, Immunologic↗