Protective role of unconjugated bilirubin on complement-mediated hepatocytolysis

Basiglio, Cecilia Lorena; Arriaga, Sandra Mónica María; Pelusa, Héctor Fabián; Almará, Adriana M.; Roma, Marcelo G.; Mottino, Aldo D.

doi:10.1016/j.bbagen.2007.03.005

Cited by 25 publications

(22 citation statements)

References 43 publications

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“…It has been known that, in the context of SLE, several antigenantibody complexes, such as nucleosomes-anti-dsDNA antibody complex, settle in the renal glomerular basement membrane, which can activate complement system and initiate the glomerulonephritis [31]. Since some previous studies indicated that bilirubin had inhibitory eVects on various complement-mediated injuries [32][33][34], we presumed that bilirubin may play a protective role in lupus renal involvement and lower serum bilirubins may be closely associated with renal involvement in SLE patients. Actually, our present study suggested although serum total bilirubin, indirect bilirubin, and direct bilirubin were all signiWcantly decreased in SLE patients with lupus renal involvement, compared with those without lupus renal involvement, only lower direct bilirubin showed a signiWcantly independent association with lupus renal involvement in SLE patients.…”

Section: Discussionmentioning

confidence: 99%

Bilirubin levels in patients with systemic lupus erythematosus: increased or decreased?

et al. 2011

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The aim of this study was to investigate the serum bilirubin levels in SLE patients and their associations with clinical and laboratory characteristics of SLE. There were 198 SLE patients in this study, of whom 7 cases with tobacco smoking or alcohol intake were excluded. Some clinical and laboratory characteristics of the patients were obtained by medical record review. In addition, 154 age- and sex- matched healthy volunteers with no histories of SLE, liver diseases, and other autoimmune or inflammatory diseases were randomly recruited into this study. The serum bilirubin levels were lower in SLE patients without liver diseases than in healthy controls (P = 0.000). Univariate logistic analysis demonstrated that hypertension, lupus renal involvement, positive anti-dsDNA antibody, C3, C4, hsCRP, and albumin remained as impact factors of total bilirubins; lupus renal involvement, ESR, IgG, globulin, and ALT, as impact factors of direct bilirubins; and lupus renal involvement, positive anti-dsDNA antibody, C3, C4, hsCRP, and albumin, as impact factors of indirect bilirubins. However, multivariate logistic analysis showed that only hsCRP remained as an independent positive impact factor of total bilirubins, lupus renal involvement as an independent negative impact factor of direct bilirubins, and hsCRP and albumin as independent positive impact factors of indirect bilirubins. In conclusion, serum bilirubin levels are decreased in SLE and the decreased bilirubin levels could be associated with inflammatory process and lupus renal involvement of SLE.

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Section: Discussionmentioning

confidence: 99%

Bilirubin levels in patients with systemic lupus erythematosus: increased or decreased?

et al. 2011

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“…Thus, unconjugated bilirubin, which is a product of heme catabolism, found at high concentrations in the case of liver diseases or of hemolytic anemia, binds to C1q and inhibits the classical complement pathway (45,46). Moreover, synthetic heterocyclic compounds such as bisphenol disulfates, sulfated steroids, and triterpenoids also inhibit the classical complement pathway at the level of C1q (47,48).…”

Section: Discussionmentioning

confidence: 99%

Heme Interacts with C1q and Inhibits the Classical Complement Pathway

Roumenina

Radanova

Атанасов

et al. 2011

Journal of Biological Chemistry

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C1q is the recognition subunit of the first component of the classical complement pathway. It participates in clearance of immune complexes and apoptotic cells as well as in defense against pathogens. Inappropriate activation of the complement contributes to cellular and tissue damage in different pathologies, urging the need for the development of therapeutic agents that are able to inhibit the complement system. In this study, we report heme as an inhibitor of C1q. Exposure of C1q to heme significantly reduced the activation of the classical complement pathway, mediated by C-reactive protein (CRP) and IgG. Interaction analyses revealed that heme reduces the binding of C1q to CRP and IgG. Furthermore, we demonstrated that the inhibition of C1q interactions results from a direct binding of heme to C1q. Formation of complex of heme with C1q caused changes in the mechanism of recognition of IgG and CRP. Taken together, our data suggest that heme is a natural negative regulator of the classical complement pathway at the level of C1q. Heme may play a role at sites of excessive tissue damage and hemolysis where large amounts of free heme are released.

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Section: Discussionmentioning

confidence: 99%