Immunoblot analysis of the eighth component of human complement

Nürnberger, W.; Seger, R; Kobler, Philipp; Mons, Ingrid; Tedesco, Francesco; Wahn, V.

doi:10.1016/0022-1759(88)90251-7

Cited by 6 publications

(1 citation statement)

References 14 publications

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“…43 The C5 antibody detected a band corresponding to the reported value for the ␤ chain, 44 whereas the C8 antibody identified a band corresponding to the ␣ chain. 45 The antibody for C5b-9 (MAC) identified a strong band in the infarcted heart and complement-activated serum of a very high molecular weight, extrapolated to about 800 kDa, which is the reported molecular weight for the MAC. 46 The presence of C3d and C4d indicates that, in infarcted tissue as well as in IgG-activated serum, the complement cascade has been activated past the opsonization phase, with the presence of the MAC establishing full activation of the pathway by assembly of the terminal components into the final product.…”

Section: Immunoblotsmentioning

confidence: 99%

Human Heart Generates Complement Proteins That Are Upregulated and Activated After Myocardial Infarction

Yasojima

Schwab

McGeer

et al. 1998

Circulation Research

142

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Abstract-In human heart, we detected mRNAs and proteins for C1q, C1r, C1s, C2, C3, C4, C5, C6, C7, C8, and C9 with the use of reverse transcriptase-polymerase chain reaction, Western blotting, and immunohistochemical techniques. We found an upregulation of both mRNAs and proteins in areas of recent and old myocardial infarctions. In both situations, the classical complement pathway was activated, with C4d, C3d, and the membrane attack complex (C5b-9) being deposited on damaged cardiac myocytes. These activated complement components were also identified on Western blots of infarcted tissue. Complement mRNAs in infarcted heart tissue were higher than those in liver, and liver complement mRNAs were not upregulated in cases with infarcted hearts. Our results establish that (1) complement proteins are endogenously produced by human heart; (2) the classical complement pathway is fully activated after myocardial infarction; (3) complement activation is directly involved in myocardial damage after ischemic insults; and (4) damage from complement activation may be chronically sustained. These data suggest that inhibition of the complement system should be effective in treating myocardial infarction. (Circ Res. 1998;83:860-869.)Key Words: complement gene expression Ⅲ classical pathway Ⅲ postmortem delay Ⅲ immunohistochemistry Ⅲ Western blotting Ⅲ liver complement T here have been many reports on association of complement proteins with myocardial damage. These include human myocardial infarcts, 1-8 as well as damaged hearts in animal models of ischemia. 8 -16 Activation of both the classical and alternative complement pathways has been reported. 17,18 Evidence that such activation is not an epiphenomenon, but contributes to tissue injury, comes directly from postmortem examination of human heart in which the membrane attack complex (MAC, C5b-9) has been identified on damaged muscle fibers. 4,7,19 It comes indirectly from animal models in which ischemic myocardial damage is ameliorated by interference with complement activation. Intervention by administration of C1 esterase inhibitor, 18,20,21 antibodies to C5a, 22 and the soluble form of CR-1 23,24 has reduced myocardial damage. The particular role of the MAC (C5b-9) comes from evidence that rabbits deficient in the complement protein C6 have a reduced infarct size in cardiac ischemiareperfusion models compared with C6-sufficient rabbits. 25 It has traditionally been assumed that liver is the source of complement proteins that participate in these events. But we have recently shown that complement proteins are produced in several organs of the body, including brain and heart. We 26 have also shown that production of C3 and C9 mRNAs and their protein products is sharply upregulated in isolated rabbit heart after reperfusion injury, and that the production by heart in this circumstance substantially exceeds that of normal liver. In brain, we 27,28 have shown that all proteins of the classical complement pathway are produced by neurons, and that this production is upregulate...

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Section: Immunoblotsmentioning

confidence: 99%

Human Heart Generates Complement Proteins That Are Upregulated and Activated After Myocardial Infarction

Yasojima

Schwab

McGeer

et al. 1998

Circulation Research

142

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Familial deficiency of the seventh component of complement associated with recurrent meningococcal infections

et al. 1989

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We describe an 11-year-old girl suffering from recurrent meningitis with a complete absence of the seventh component of complement (C7). Diagnosis was established by haemolytic titration and western blotting. The patient's serum lacked the 85 kDa C7 chain. Haemolytic activity of serum was reconstituted with either pooled normal human serum or with purified C7. The relatives (parents and one sister) had half-normal levels of both immunochemically and functionally determined C7, indicating a heterozygous state for C7 deficiency.

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Neurons express proteins of the classical complement pathway in Alzheimer disease

et al. 1997

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Immunoblot analysis of the eighth component of human complement

Cited by 6 publications

References 14 publications

Human Heart Generates Complement Proteins That Are Upregulated and Activated After Myocardial Infarction

Human Heart Generates Complement Proteins That Are Upregulated and Activated After Myocardial Infarction

Familial deficiency of the seventh component of complement associated with recurrent meningococcal infections

Neurons express proteins of the classical complement pathway in Alzheimer disease

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