Hepatitis ; immunology ; Humans ; Liver Cirrhosis ; immunology ; Receptors, Complement ; blood

B cell activated co-receptor plays important roles in linkage of innate and acquired humoral immune responses. CD21 molecule in the co-receptor complex is a receptor for C3dg and CD19 molecule enhances BCR signal transduction. CD21 also expresses on the surface of follicular dendritic cells, which mediates the long-term maintenance of antigens and is indispensable for maintaining the memory of B cells. B cell activated co-receptor also has an effect on the negative selection of B cells reactive to autoantigens.
Animals ; Antigens, CD19 ; immunology ; Autoantigens ; immunology ; B-Lymphocytes ; immunology ; Humans ; Receptors, Complement 3d ; immunology ; Receptors, Immunologic

Hyperacute rejection (HAR) is the major obstacle to xenotransplantation. In HAR complement (C') cascade is activated following the binding of xenoreactive antibodies to the donor tissue. Complement receptor type 1 (CR1), the most efficient protein in inhibiting activated C's, was modified with membrane cofactor protein (MCP) to make a more efficient C'-inhibiting hybrid molecule. Modification was done by swapping the four active site short consensus repeats (SCRs) of MCP for the SCRs 8-11 of CR1. The hybrid molecule (CR1/MCP) was expressed on the surface of mouse L cells. When the complement inhibitory activity of the CR1/MCP protein was compared with that of the wild CR1 (wCR 1) protein, CR1/MCP's inhibitory activity was weaker than wCR1's. CR1/MCP protein's L cell protecting activity from complement's attack was more prominent in adherent state than in suspension state. From these results it was suggested that the conformational direction of MCP's inhibitory action on C' is different from that of CR1 and most of the MCP expression seems to be confined to the apical side but not to the basal side of the L cell in adherent state. The wCR1's expression seems to be present on all sides of the L cell. Finally, the inverted direction of SCRS-11 of CR1 or variable length of the serine-threoninrich structure of MCP could be tried to make other CR1/MCP variants with more powerful C' inhibitory activities.
Animals ; Antibodies ; Antigens, CD46 ; Catalytic Domain ; Complement System Proteins* ; Consensus ; Humans ; Mice ; Receptors, Complement ; Tissue Donors ; Transplantation, Heterologous

The complement system is a key component of innate immunity. More than 45 genes encoding the proteins of complement components or their isotypes and subunits, receptors, and regulators have been discovered. These genes are distributed throughout different chromosomes, with 19 genes comprising three significant complement gene clusters in the human genome. Genetic deficiency of any early component of the classical pathway (C1q, C1r/s, C2, C4, and C3) is associated with autoimmune diseases due to the failure of clearance of immune complexes (IC) and apoptotic materials, and the impairment of normal humoral response. Deficiencies of mannan-binding lectin (MBL) and the early components of the alternative (factor D, properdin) and terminal pathways (from C3 onward components: C5, C6, C7, C8, C9) increase susceptibility to infections and their recurrence. While the association of MBL deficiency with a number of autoimmune and infectious disorders has been well established, the effects of the deficiency of other lectin pathway components (ficolins, MASPs) have been less extensively investigated due to our incomplete knowledge of the genetic background of such deficiencies and the functional activity of those components. For complement regulators and receptors, the consequences of their genetic deficiency vary depending on their specific involvement in the regulatory or signalling steps within the complement cascade and beyond. This article reviews current knowledge and concepts about the genetic load of complement component deficiencies and their association with diseases. An integrative presentation of genetic data with the latest updates provides a background to further investigations of the disease association investigations of the complement system from the perspective of systems biology and systems genetics.
Animals ; Complement Activation ; genetics ; Complement System Proteins ; deficiency ; genetics ; HLA Antigens ; genetics ; Humans ; Immunity, Innate ; genetics ; Immunologic Deficiency Syndromes ; genetics ; Lectins ; metabolism ; Multigene Family ; Receptors, Complement ; genetics

China ; Ethnic Groups ; genetics ; Female ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Receptors, Complement ; genetics

Animals ; Beverages ; Macrophages ; drug effects ; metabolism ; Mice ; Mice, Inbred Strains ; Receptors, Complement 3b ; metabolism

In the intestinal mucosal surface, microfold cells (M cells) are the representative gateway for the uptake of luminal antigens. At the same time, M cells are the primary infection site for pathogens invading mucosal surface for their infection. Although it is well recognized that many mucosal pathogens exploit the M cells for their infection, the mechanism to infect M cells utilized by pathogens is not clearly understood yet. In this study, we found that M cells expressing complement 5a (C5a) receptor (C5aR) also express Toll-like receptor (TLR) 1/2 and TLR4. Infection of Yersinia enterocolitica, an M cell-invading pathogen, synergistically regulated cyclic adenosine monophosphate-dependent protein kinase A (cAMP-PKA) signaling which are involved in signal crosstalk between C5aR and TLRs. In addition, Y. enterocolitica infection into M cells was enhanced by C5a treatment and this enhancement was abrogated by C5a antagonist treatment. Finally, Y. enterocolitica infection into M cells was unsuccessful in C5aR knock-out mice. Collectively, we suggest that exploit the crosstalk between C5aR and TLR signaling is one of infection mechanisms utilized by mucosal pathogens to infect M cells.
Adenosine ; Animals ; Complement C5a* ; Complement System Proteins* ; Cyclic AMP-Dependent Protein Kinases ; Mice ; Mice, Knockout ; Phenobarbital ; Receptor, Anaphylatoxin C5a* ; Toll-Like Receptors* ; Yersinia enterocolitica* ; Yersinia*

OBJECTIVETo investigate the role of sulfated tyrosine in regulating the activity of tyrosylprotein sulfotransferases (TPST) 1 and TPST2.

METHODSConstructs of TPST 1 and TPST2 were amplified by polymerase chain reaction (PCR), then fused into immunoglobulin G1 Fc region. All the variants in which sulfated tyrosines were mutated to phenylalanine were made by the PCR-based Quick Change method and confirmed by sequencing the entire reading frame. Small hairpin RNA (shRNA) constructs-targeting nucleotides 259-275 of TPST1 and nucleotides 73-94 of TPST2 were generated and subcloned into pBluescript. Human embryonic kidney (HEK) 293T cells were transfected with these plasmids. One day later, cells were split: one part was labeled with 35S-cysteine and methionine or 35S-Na2SO3 overnight, the second part was used for 125I labeled binding experiment, and the third part was retained for binding and flow cytometry.

RESULTSTyrosines at position 326 of TPST1 and position 325 of TPST2 were sulfated posttranslationally. Tyrosine sulfation of TPSTs was effectively inhibited by sulfation inhibitors, including specific shRNAs and non-specific NaCIO3. shRNAs reduced the sulfation of C3a receptor and C5a receptor, and partially blocked the binding of these two receptors to their respective ligands.

CONCLUSIONSThe activities of TPSTs were regulated by tyrosine sulfation. Inhibition of sulfotyrosine decreases the binding ability of C3a receptor and C5a receptor to their respective ligands.

Cell Line ; Complement C3a ; metabolism ; Complement C5a ; metabolism ; Humans ; Protein Binding ; Protein Processing, Post-Translational ; Receptor, Anaphylatoxin C5a ; metabolism ; Receptors, Complement ; metabolism ; Sulfotransferases ; genetics ; metabolism ; Transfection ; Tyrosine ; analogs & derivatives ; metabolism

Abdominal Neoplasms ; complications ; metabolism ; pathology ; surgery ; Adult ; Dendritic Cell Sarcoma, Follicular ; complications ; metabolism ; pathology ; surgery ; Diagnosis, Differential ; Female ; Humans ; Ki-1 Antigen ; metabolism ; Leukocytosis ; complications ; metabolism ; pathology ; surgery ; Receptors, Complement 3b ; metabolism ; Receptors, Complement 3d ; metabolism ; Young Adult

OBJECTIVETo study the clinical pathological features and immunophenotype of follicular dendritic cell sarcoma (FDCS) with discussion on its diagnostic clues to improve diagnostic level.

METHODSFive cases of FDCS were analyzed by clinical, pathologic and immunohistochemistry methods.

RESULTSFive cases of FDCS were located in the cervical lymph node. Microscopically, the normal architectures were effaced by ovoid, spindle-shaped with fascicular, diffuse or whorled patterns and with rich lightly eosinophilic cytoplasm, syncytial appearance. Nuclei tend to show irregular clustering, scattered multinucleated giant cell. Nucleoli often distinct, sometimes prominent. Mitotic count variable, may show significant cellular pleomorphism. Immunohistochemical studies show that the tumor cells were positive for CD21, CD35, but negative for CD1a, CD34, CK and HMB45. Under electron microscopy, the tumor cells possessed long villus cytoplasmic processes and desmosome-like junctions, Birbeck granules were absent.

CONCLUSIONSFDCS is a rare malignant tumor and differential diagnosis includes Langerhans cell sarcoma, interdigitating dentric cell sarcoma, malignant fibrous histocytoma, melanoma, metastatic spindle cell carcinoma and others. Immunohistochemistry and electron microscopy are necessary for a correct diagnosis.

Adult ; Dendritic Cell Sarcoma, Follicular ; metabolism ; pathology ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Lymph Nodes ; metabolism ; pathology ; ultrastructure ; Male ; Microscopy, Electron ; Middle Aged ; Receptors, Complement 3b ; metabolism ; Receptors, Complement 3d ; metabolism