The effects of complement C3f segment on expression and secretion of collagen I, III and transforming growth factor-beta1 in human embryonic lung fibroblast / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To observe the effects of complement fragment C3f on expression and secretion of collagen I, III and transforming growth factor( TGF)-beta1 in human embryonic lung fibroblast (MRC-5) cells.</p><p><b>METHODS</b>MRC-5 cells were cultured with C3f (the synthetic 17 peptides fragments of complement C3). The extracellular and intracellular expression levels of type I, III collagens and TGF-beta1 in MRC-5 cultures were detected by ELISA and immunohistochemistry, respectively.</p><p><b>RESULTS</b>The expression levels of type I, III collagen and TGF-beta1 in the supernatant of MRC-5 cultures decreased significantly with the concentrations of C3f as compared with controls (P < 0.05). Also the expression level of TGF-beta1 in MRC-5 cytoplasm reduced significantly as compared with controls (P < 0.05).</p><p><b>CONCLUSION</b>The results of present in vitro study showed that the complement fragment C3f could reduce the formation of TGF-beta1 and type I, III collagens in MRC-5 cells, and inhibit the lung tissue fibrosis.</p>

The class A macrophage scavenger receptor type I (SR-AI) recognizes complement iC3b and mediates NF-κB activation

The macrophage scavenger receptor SR-AI binds to host tissue debris to perform clearance and it binds to bacteria for phagocytosis. In addition, SR-AI modulates macrophage activation through cell signaling. However, investigation of SR-AI signaling on macrophages is complicated due to its promiscuous ligand specificity that overlaps with other macrophage receptors. Therefore, we expressed SR-AI on HEK 293T cells to investigate its ligand binding and signaling. On 293Tcells, SR-AI could respond to E. coli DH5α, leading to NF-κB activation and IL-8 production. However, this requires E. coli DH5α to be sensitized by fresh serum that is treated with heat-inactivation or complement C3 depletion. Anti-C3 antibody inhibits the binding of SR-AI to serum-sensitized DH5α and blocks DH5α stimulation of SR-AI signaling. Further analysis showed that SR-AI can directly bind to purified iC3b but not C3 or C3b. By mutagenesis, The SRCR domain of SR-AI was found to be essential in SR-AI binding to serum-sensitized DH5α. These results revealed a novel property of SR-AI as a complement receptor for iC3b-opsonized bacteria that can elicit cell signaling.

Action of chlorogenic acid on the complement system

Previous research on plants used in folk medicine as antidotes against snake-bite revealed some constituents responsible for such protection. Chlorogenic acid (3-0-caffeoyl quinic acid) was one of these substances, studied with more attention. It has been shown that this substance binds to proteins through hydrophobic interactions and hydrogen bonds. This paper shows the preliminary results about the anti-complementary action of chlorogenic acid. Human and guinea pig sera, treated with chlorogenic acid, were added to the hemolytic system (sheep erythrocyte sensitized with hemolysin) to study its effect on the activation of the classical complement pathway. The action on the alternative pathway was studied with human serum treated with chlorogenic acid and zymosan. Our results show that chlorogenic acid presents anti-complementary action at the classical pathway, since the sera are not able to lysis the indicator system. The presence of C3b fragments on the surface of the yeast cells demonstrates that the alternative pathway was not affected.

Expression of iC3b Receptor on Candida albicans and Its Role on Adhesion of the Yeast to Human Dermal Microvascular Endothelium / 대한의진균학회지

BACKGROUND: The adherence of microorganisms to host tissue is an important process in the pathogenesis of fungal infection. A protein that shares antigenic and structural homology with the alpha-subunit of leukocyte adhesion glycoprotein CD11b/CD18, also known as iC3b receptor, Mo-1 or Mac-1, has been isolated from the surface of C. albicans. OBJECTIVE: This study was done to observe the changes in the expression of iC3b receptor on C. albicans by glucose or immunosuppressive agents and to elucidate the effect of glucose and anti-iC3b receptor antibodies on adhesion between human dermal microvascular endothelial cells(HDMEC) and C. albicans. METHODS: We utilized immunofluorescence study and immunofluorescent flow cytometry and the binding assay of C. albicans to cultured HDMEC in vitro and blocking assay using monoclonal antibody were performed. RESULTS: Immunofluorescence study and immunofluorescent flow cytometric analysis demonstrated surface expression of iC3b receptor on C. albicans. The expression of surface iC3b receptor on C. albicans in creased in a dose dependent manner with increasing concentrations of glucose, cyclophosphamide and prednisolone. The adherence of C. albicans to HDMEC correlated positively with glucose levels. The adherence of C. albicans to HDMEC decreased significantly by the treatment with anti-iC3b receptor antibodies. CONCLUSION: The results suggest that iC3b receptors should be involved in the adherence of C. albicans to vascular endothelial cells and may be involved in the pathogenesis of hematogenous candidiasis

Novel mechanisms of immune evasion by Schistosoma mansoni

The interaction of Schistosoma mansoni with its host's immune system is largely affected by multiple specific and non-specific evasion mechanisms employed by the parasite to reduce the host's immune reactivity. Only little is known about these mechanisms on the molecular level. The four molecules described below are intrinsic parasitic proteins recently identified and studied in our laboratory. 1. m28--A 28kDa membrane serine protease. m28 cleaves iC3b and can thus restrict attack by effector cells utilizing complement receptors (especially CR3). Treatment with protease inhibitors potentiates killing of schistosomula by complement plus neutrophils. 2. Smpi56--A 56kDa serine protease inhibitor. Smpi56 binds covalently to m28 and to neutrophil's elastase and blocks their proteolytic activity. 3. P70--A 70kDa C3b binding protein. The postulated activity of P70 includes binding to C3b and blocking of complement activation of the C3 step. 4. SCIP-1--A 94kDa schistosome complement inhibitor. SCIP-1 shows antigenic and functional similarities to the human 18kDa complement inhibitor CD59. Like CD59, SCIP-1 binds to C8 and C9 and blocks formation of the complement membrane attack complex. Antibodies directed to human CD59 bind to schistosomula and potentiate their killing by complement. The structure and function of these four proteins as well as their capacity to induce protection from infection with S. mansoni are under investigation.

Requirements of Opsono-phagocytosis of staphylococci

Opsonophagocytosis of both Staph. aureus and coagulase negative staphylococci was studied in 46 strains from different sources of infection. Opsonophagocytosis was found to be mediated by the antibody and complement [in normal human serum] but could be also mediated by antibody alone in absence of the complement [in heated serum]. Also, it could be mediated by the complement alone in the absence of the antibody [in absorbed serum]. Coagulase negative staphylococci was more susceptible to opsonophagocytosis than Staph. aureus strains. No difference in opsonophagocytosis was found according to difference of sources of isolation

The possible mechanism of action of IgG antibodies and platelets protecting against Trypanosoma cruzi infection

1. The role of IgG antibody and platelets in the mechanism of defense against Trypanosoma cruzi infection is reviewed. 2. Experimental data showing the participation of the different IgG subclasses in the immune lysis and immune clearance of the parasites are discussed. 3. The involvement of the platelets in the removal of the parasites from the circulation is considered. 4. It is suggested that IgG anti-T. cruzi antibodies interact with circulating parasites leading to formation of microaggregates, activation of C3 and deposition of C3 and deposition of C3b on the immune aggregates followed by adherence of platelets through C3b receptors. The immune aggregates would then be taken up by cells of the mononuclear phagocytic system

Reactividad del receptor eritrocitario CR1 en pacientes con lupus eritematoso sistémico / Erythrocyte CR1 receptor reactivity in patients with systemic lupus erythematosus

Se estudia la reactividad del receptor CR1 eritrocitario, por su capacidad de inmunoadherencia-hemoaglutinación (IAH) frente a distintas concentraciones de gamaglobulina humana agregada en presencia de suero fresco de cobayo como fuente de complemento, en glóbulos rojos de 80 voluntarios sanos y 42 pacientes con lupus eritematoso sistémico. Por este método se detecta reactividad del receptor CR1 en un 87,5% de la población sana versus un 35,7% de la población lúpica. Ambas poblaciones presentan una distribución trimodal de los títulos de IAHA. El 72,5% de la población sana se distribuye en el grupo de reactividad intermedia y 64,3% de la población lúpica en el de reactividad baja, en concordancia con otros autores que describen tres grupos fenotípicos. No se encuentra correlación entre la expresión defectuosa del CR1 y los parámetros convencionales de actividad. Este receptor eritrocitario comprometido en el procesamiento de inmunocomplejos, que constituye el 95% del CR1 circulante, es un factor más que contribuye a la fisiopatología de la enfermedad cuando su reactividad es defectuosa

Vasculopatia aguda do transplante renal / Acute vasculopathy of renal transplantation

Os autores descrevem um tipo peculiar de rejeiçäo de caráter humoral que ocorreu em 14 casos, num total de 284 transplantes realizados na Unidade de Transplante Renal do Hospital das Clínicas da Faculdade de Medícina da Universidade de Säo Paulo. O quadro anátomo-patológico se caracteriza por uma importante endarterite obliterqante, que acomete principalmente artérias arqueadas ou arteríolas localizadas próximo a área justa-medular. Necrose tribular aguda de caráter focal e sem evidências de regeneraçäo é um achado constante. A imunoflurorescência evidencia deposiçäo de IgM e fibrinogênio na íntima dos vasos acometidos com intensidade variável. C3 também pode ser detectado em menor quantidade e intensidade. Do ponto de vista clínico se caracteriza por uma rejeiçäo grave, precoce, que näo responde a pulsoterapia e com perda precoce do enxerto em 12 dos 14 casos observados