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PubMed2001

Generation of C-reactive protein and complement components in atherosclerotic plaques.

C-reactive protein (CRP) and complement are hypothesized to be major mediators of inflammation in atherosclerotic plaques. We used the reverse transcriptase-polymerase chain reaction technique to detect the mRNAs for CRP and the classical complement components C1 to C9 in both normal arterial and plaque tissue, establishing that they can be endogenously generated by arteries. When the CRP mRNA levels of plaque tissue, normal artery, and liver were compared in the same cases, plaque levels were 10.2-fold higher than normal artery and 7.2-fold higher than liver. By Western blotting, we showed that the protein levels of CRP and complement proteins were also up-regulated in plaque tissue and that there was full activation of the classical complement pathway. By in situ hybridization, we detected intense signals for CRP and C4 mRNAs in smooth muscle-like cells and macrophages in the thickened intima of plaques. By immunohistochemistry we showed co-localization of CRP and the membrane attack complex of complement. We also detected up-regulation in plaque tissue of the mRNAs for the macrophage markers CD11b and HLA-DR, as well as their protein products. We showed by immunohistochemistry macrophage infiltration of plaque tissue. Because CRP is a complement activator, and activated complement attacks cells in plaque tissue, these data provide evidence of a self-sustaining autotoxic mechanism operating within the plaques as a precursor to thrombotic events.

Aged↗
PubMed1998

Shark complement: an assessment.

The classical (CCP) and alternative (ACP) pathways of complement activation have been established for the nurse shark (Ginglymostoma cirratum). The isolation of a cDNA clone encoding a mannan-binding protein-associated serine protease (MASP)-1-like protein from the Japanese dogfish (Triakis scyllia) suggests the presence of a lectin pathway. The CCP consists of six functionally distinct components: C1n, C2n, C3n, C4n, C8n and C9n, and is activated by immune complexes in the presence of Ca++ and Mg++ ions. The ACP is antibody independent, requiring Mg++ ions and a heat-labile 90 kDa factor B-like protein for activity. Proteins considered homologues of C1q, C3 and C4 (C2n) of the mammalian complement system have been isolated from nurse shark serum. Shark C1q is composed of at least two chain types each showing 50% identity to human C1q chains A and B. Partial sequence of the globular domain of one of the chains shows it to be C1q-like rather than like mannan-binding protein. N-terminal amino acid sequences of the alpha and beta chain of shark C3 and C4 molecules show significant identity with corresponding human C3 and C4 chains. A sequence representing shark C4 gamma chain, shows little similarity to human C4 gamma chain. The terminal shark components C8n and C9n are functional analogues of mammalian C8 and C9. Anaphylatoxin activity has been demonstrated in activated shark serum, and porcine C5a desArg induces shark leucocyte chemotaxis. The deduced amino acid sequence of a partial C3 cDNA clone from the nurse shark shows 50%, 30% and 24% homology with the corresponding region of mammalian C3, C4 and alpha 2-macroglobulin. Deduced amino acid sequence data from partial Bf/C2 cDNA clones, two from the nurse shark and one from the Japanese dogfish, suggest that at least one species of elasmobranch has two distinct Bf/C2 genes.

Amino Acid Sequence↗
PubMed1992

Trichinella spiralis: activation of complement by infective larvae, adults, and newborn larvae.

The ability of Trichinella spiralis to activate complement (C) has been addressed by several investigators. However, these investigators employed methods in which either detection of C fragments on the parasite surface or the adherence of leukocytes to the parasite was considered an indication of C activation. The present studies were undertaken to examine: (a) whether activation of C occurs via the classical and/or alternative pathway, (b) at which stage(s) of the parasite C activating capacity is acquired, and (c) what molecular entities of the epicuticle and/or cuticle are responsible for initiating C activation. Our studies indicate that T. spiralis activates C primarily via the alternative pathway (and weakly via the classical pathway) since incubation of parasites obtained from infected mice with either normal human serum (NHS) or Mg.EGTA-NHS, followed by incubation (1 hr, 37 degrees C) with antibody-sensitized sheep erythrocytes or rabbit erythrocytes, respectively, showed a time-and parasite number-dependent depletion of C. Although the three stages of T. spiralis, i.e., infective larvae, adults and newborn larvae, are capable of activating C, the newborn appears to be the most potent activator, especially when parasite number and size are taken into consideration. Further evidence of C activation is obtained from SDS-PAGE and Western blot analysis in which homogenates of parasites preincubated with NHS showed the presence of C3, C9, and C1q, whereas controls without serum were negative. Since isolated C1q was also capable of directly binding to the surface of adults and infective larvae, it is postulated that their cuticle and/or epicuticle may possess surface structures which serve as binding sites for C1q.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Quantification of the terminal complement complex in human plasma by an enzyme-linked immunosorbent assay based on monoclonal antibodies against a neoantigen of the complex.

The fluid-phase terminal complement complex (TCC), consisting of the components C5b, C6, C7, C8, C9, and the S-protein, has recently been detected in normal human plasma by using antibodies against native terminal complement components. Increased amounts of TCC were then found in several patients with in vivo activation of complement. We now describe a sensitive, specific, and reliable enzyme-linked immunosorbent assay for quantification of the TCC, based on monoclonal antibodies against a neoantigen of the complex. The results indicate that the TCC is present in normal human plasma and in increased amounts in patients with complement activation in vivo, thus confirming previously obtained results. The assay is easy to perform and can be used for examination of large numbers of plasma samples.

Antibodies, Monoclonal↗
PubMed2004

CD59a deficiency exacerbates ischemia-reperfusion injury in mice.

The terminal complement components C5a and the membrane attack complex are involved in the pathogenesis of ischemia-reperfusion injury in many organs. CD59 is the major regulator of membrane attack complex formation. Mice deficient in the Cd59a gene (mCd59a-/-) were used to investigate the role of CD59 in renal ischemia-reperfusion injury. Unilateral ischemia-reperfusion injury was induced by clamping the left renal pedicle for 30 minutes under general anesthetic. Mice were studied at 72 hours and 2 weeks after ischemia-reperfusion injury. mCd59a-/- mice developed significantly greater tubular injury (P = 0.01), tubulointerstitial apoptosis (P = 0.02), and neutrophil influx (P = 0.04) than controls at 72 hours after ischemia-reperfusion. Two weeks after ischemia-reperfusion, mCd59a-/- mice exhibited more severe tubular damage predominantly in a corticomedullary distribution than controls (P = 0.02). Quantification of interstitial leukocytes revealed significantly greater numbers of infiltrating lymphocytes (but not macrophages) in mCd59a-/- mice than controls (P = 0.04) at 2 weeks. At both time points, significantly more C9 (as a marker of membrane attack complex) deposition occurred in a peritubular distribution in mCd59a-/- mice than controls. In conclusion, these results demonstrate that the lack of CD59a, by allowing unregulated membrane attack complex deposition, exacerbates both the tubular injury and the interstitial leukocyte infiltrate after ischemia-reperfusion injury in mice.

Animals↗
PubMed1981

Hemolytic complement and its components in Syrian hamsters: a study of five strains uninfected and infected with Brugia pahangi.

Complement profiles were tested in outbred (LVG) Syrian hamsters (Mesocricetus auratus) and compared to the MHA, LHC, PD4, and CB inbred strains. The total C and C component concentrations in the sera varied among the strains and were in the following ranges in untreated animals (in CH50 units per ml): total C, 140-260 (undetectable in PD4 and CB); Cl, 14,000-25,000; C2, 200-800 (except PD 4 and CB); C3, 40,000 and 80,000; C4, 2,000-2,800 (except PD4 and CB); C4, 40,000-80,000; C6, 3,600-6,000 (undetectable in PD4 and CB); C7, 50,000-350,000; C8, 10,000-30,000; C9, 30,000-60,000. The PD4 and CB strains had undetectable total C and C6, and their exact C2 and C4 levels could not be determined, but were lower than in the other strains. The MHA strain had the highest total C levels, but had significantly lower (1/3 or less) C7 levels than the other strains of hamsters. Infection of hamsters with the filarid nematode Brugia pahangi for four to five months produced moderate decreases in the total C and C3 levels, but varied changes in other C components. Six infected and three uninfected animals died during the experiment from spontaneous enteritis and weight loss.

Animals↗
PubMed1983

Recurrent meningococcal meningitis due to partial complement defects and poor anti-meningococcal antibody response.

An otherwise healthy young man had three episodes of meningococcal meningitis within three years. The last episode was caused by group A, and occurred four weeks after the patient received group A vaccine, thus representing one of the very few failures of this vaccine. The specific susceptibility to meningococcal infections was connected with half-normal levels of several components of the complement system (C3, C4, C9, factor B, properdin), and reduced antibody responses to group A and group C meningococcal polysaccharides, but not to several other polysaccharide or protein antigens.

Adolescent↗
PubMed1978

The requirement of specific antibody for the killing of E. coli by the alternate complement pathway in bovine serum.

Experiments using the selective divalent cation chelator, ethylene glycol tetraacetic acid (EGTA) showed that the alternate complement pathway was involved in the bactericidal action of bovine serum on two strains of E. coli. The bactericidal system was shown, in experiments involving EGTA and epsilon-amino caproic acid, to be independent of Ca++ and the C1 unit of complement. The fixation of the complement components C3-C9 by endotoxin does not require a functional classical pathway ((C1, C4 and C2). In the case of one coliform strain (W1) however, there was an almost total dependence on a factor absorbable at 0 degrees with homologous bacteria, and which appeared to be a natural antibody. These results suggest that in certain circumstances in the cow, gamma globulins may be directly involved in the activation of the alternate complement pathway.

Animals↗
PubMed1982

An amphiphilic structure of the ninth component of human complement. Evidence from analysis of fragments produced by alpha-thrombin.

Purified human C9 was treated separately with three proteolytic enzymes: trypsin, plasmin, and alpha-thrombin, and the digestion products were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Trypsin initially cleaved the Mr = 71,000 C9 to produce a Mr = 47,000 fragment plus numerous smaller fragments and prolonged digestion reduced the molecule to small polypeptides. Plasmin produced a Mr = 37,000 fragment which was stable to further digestion, plus fragments smaller than Mr = 10,000. Human alpha-thrombin cleaved C9 (7.8% carbohydrate) at a single internal site to produce a Mr = 37,000 fragment (11.3% carbohydrate) and a Mr = 34,000 fragment (3.9% carbohydrate). Statistical analysis of the amino acid compositions of the fragments and alkaline polyacrylamide gel electrophoresis showed that C9 is highly amphiphilic; the Mr = 34,000 fragment contains a majority of the acidic amino acids and migrates rapidly on alkaline gels; the Mr = 37,000 fragment is hydrophobic with a slow electrophoretic mobility. The two fragments remain noncovalently associated, but were separated by sodium dodecyl sulfate-hydroxylapatite chromatography. The NH2-terminal sequence analysis of native C9, of alpha-thrombin-cleaved C9, and for the isolated fragments showed that the acidic Mr = 34,000 fragment is the NH2-terminal C9a domain and the more hydrophobic Mr = 37,000 fragment is the carboxyl-terminal C9b domain. Hemolytic activity of C9 was unaffected by alpha-thrombin cleavage.

Amino Acid Sequence↗
PubMed1970

Reactive lysis: the complement-mediated lysis of unsensitized cells. II. The characterization of activated reactor as C56 and the participation of C8 and C9.

It has been shown that the "activated reactor" that is produced in certain human sera by complement activation is a stable complex of the fifth and sixth component of complement (C56). On interaction with C7, the indicator factor, a complex C567 is formed which for a short time (half-life less than 1 min) has an activated binding site and can attach itself to normal red cell membranes, conferring on them the hemolytic properties of the "heat stable" complement intermediate EC 1 approximately 7, the capacity to be lysed by C8 and C9. These cells have neither antibody nor the complement components up to C3 bound on them. The binding site-activated C567c-can similarly bind to other hydrophobic surfaces, including agarose gel where it forms a "stainable line". If the complex is not bound to a surface, the binding site decays and the resulting complex will no longer give rise to lysis. However it will still inactivate C8 and C9 in solution. The sera that can generate activated reactor apparently do so because they have an excess of C5 and C6, compared to their content of C7. The phenomenon of reactive lysis thus represents complement-mediated lysis of unsensitized cells initiated at the C5 stage by a stable complex (C56) which was generated by complement activation at a distance. The immunochemistry of the phenomenon is described and some of its implications discussed.

Animals↗
PubMed1985

The relationship between channel size and the number of C9 molecules in the C5b-9 complex.

We have recently shown by dose-response analyses with resealed erythrocyte ghosts that the channel formed by complement is a monomer of C5b-9 of the composition C5b61C71C81C9n, in which n = 1 for channels permitting passage of sucrose (0.9 nm molecular diameter) and n = 2 for channels allowing transit of inulin (3 nm molecular diameter) (1). We have now continued these experiments and expanded them by including ribonuclease A (molecular diameter, 3.8 nm) as a marker to assess whether additional C9 molecules enlarge the functional C5b-9 channel. Our results show that formation of C5b-9 channels displays one-hit characteristics with respect to C5b6 when tested by transmembrane passage of inulin or ribonuclease A. By contrast, analysis of dose-response curves of C9 indicate that n = 2-3 for channels allowing transit of inulin and n = 4 for channels allowing transit of ribonuclease A. We have also performed sieving experiments with ghosts carrying C5b-7 and containing two small markers, inositol and sucrose. Dose-response curves for C8 were performed in the presence of excess C9 to ensure conversion of all C5b-8 to C5b-9 channels. The results indicate that small channels (approximately 0.8 nm effective diameter) are not formed at high C9 multiplicity, thus confirming the results obtained with the larger markers, i.e., increase of C9 input leads to formation of larger channels.

Animals↗
PubMed1994

Time course of complement activation and inhibitor expression after ischemic injury of rat myocardium.

Activation of the complement (C) system has been documented in both experimental and clinical studies of myocardial infarction, but the exact time course and mechanisms leading to C activation have remained unclear. Our earlier postmortem study on human beings showed that formation of the membrane attack complex (MAC) of C was associated with loss of CD59 (protectin), an important sarcolemmal regulator of MAC, from the infarcted area. The recent discovery of a rat analogue of CD59 has now allowed the first experimental evaluation of the temporal and spatial relationship between C component deposition and loss of CD59 in acute myocardial infarction (AMI). After ligating the left coronary artery in rats the earliest sign of C activation, focal deposition of C3, was observed at 2 hours. Deposition of the early (C1, C3) and late pathway (C8, C9) components in the AMI lesions occurred at 3 hours. Glycophosphoinositol-anchored rat CD59 was expressed in the sarcolemmal membranes of normal cardiomyocytes. In Western blot analysis extracts of normal rat heart CD59 appeared as a band of 21 kd of molecular weight under nonreducing conditions. Loss of CD59 in the AMI lesions was observed in association with deposits of MAC from day one onward. Our results show that C activation universally accompanies AMI in vivo. It is initiated within 2 hours after coronary artery obstruction via deposition of C3, which may be due to generation of the alternative pathway C3 convertase in the ischemic area. Deposition of C1 and late C components also starts during the early hours (2 to 4 hours) after ischemia. Subsequent loss of the protective CD59 antigen may initiate postinjury clearance of the irreversibly damaged tissue.

Animals↗
PubMed2000

Properdin, the positive regulator of complement, is highly C-mannosylated.

Properdin is the positive regulator of the alternative pathway of complement activation. The 53-kDa protein is essentially composed of six thrombospondin type 1 repeats, all of which contain the WXXW motif, the recognition sequence for C-mannosylation. C-Mannosylation is a post-translational modification of tryptophan residues in which, in contrast to the well known N- and O-glycosylation, the carbohydrate is attached via a C-C bond to C-2 of the indole moiety of tryptophan. C-Mannosylation was first found in human RNase 2 and interleukin-12. The terminal complement proteins C6-C9 also carry this modification as part of their thrombospondin type 1 repeats. We studied the C-mannosylation pattern of human properdin by mass spectrometry and Edman degradation. Properdin contains 20 tryptophans of which 17 are part of a WXXW motif. Fourteen tryptophans were found to be modified 100%. This is the first example of a protein in which the majority of tryptophan residues occurs in the C-mannosylated form. These results show that C-mannosylated proteins occur at several steps along the complement activation cascade. Therefore, this system would be ideal to investigate the function of C-mannosylation.

Amino Acid Sequence↗
PubMed1978

Binding of activated properdin to untreated erythrocytes: a new function of activated properdin.

Activated human properdin was found to be capable of binding to rabbit and sheep erythrocytes to form new intermediate cells of the alternative pathway of the complement system. The intermediate cells, termed EP, can react with B, D and C3 to form other intermediate cells, tentatively termed EPB(D)C3, which can be lysed by the subsequent action of six late-acting complement components, C3 to C9. The possibility of participation of C3, B, D or immunoglobulin in the formation of EP cells was neglected by the experiments in which the inhibition of the reactivities of P or EP by antisera to P, C3, B, D or immunoglobulins were investigated. The reduction in reactivities of P to E, or of EP to B, D and C3 was observed only when pretreated with antiserum to P. Furthermore, EP cells were agglutinated only by anti-P, not by antisera to C3 or IgG. The other possibility of participation of the classical complement components such as antibody, C1, C4 and C2 in the formation of EPB(D)C3 was excluded by the non-reactivities of EP with C4 and C2 and of EAC1 with B, D and C3. Thus, activated properdin is likely to function not only as modulator of preformed enzyme such as C3bBb but also as one of early-acting components of the alternative pathway.

Agglutination↗
PubMed2006

Complement activation in the Parkinson's disease substantia nigra: an immunocytochemical study.

BACKGROUND: Inflammatory processes are increased in the Parkinson's disease (PD) brain. The long-term use of nonsteroidal anti-inflammatory drugs has been associated, in retrospective studies, with decreased risk for PD, suggesting that inflammation may contribute to development of this disorder. The objective of this study was to determine the extent of complement activation, a major inflammatory mechanism, in PD. METHODS: Substantia nigra specimens from young normal subjects (n = 11-13), aged normal subjects (n = 24-28), and subjects with PD (n = 19-20), Alzheimer's disease (AD; n = 12-13), and dementia with Lewy bodies (DLB; n = 9) were stained for iC3b and C9, representing early- and late-stage complement activation, respectively. Numbers of iC3b+, C9+, and total melanized neurons in each section were counted in a blinded fashion. Nonparametric analyses were used to evaluate differences between groups and to evaluate correlations between complement staining, numbers of melanized neurons, and the duration of PD. RESULTS: Lewy bodies in both PD and DLB specimens stained for iC3b and C9. Staining was also prominent on melanized neurons. The percentage of iC3b+ neurons was significantly increased in PD vs. aged normal and AD specimens, and in young normal vs. aged normal specimens. C9 immunoreactivity was significantly increased in PD vs. AD specimens, but unlike iC3b, the increased C9 staining in PD and young normal specimens did not achieve statistical significance vs. aged normal specimens. iC3b and C9 staining in PD specimens was not correlated with the numbers of remaining melanized neurons, nor with the duration of PD. CONCLUSION: Complement activation occurs on Lewy bodies and melanized neurons in the PD substantia nigra. Early complement activation (iC3b) is increased on melanized neurons in PD vs. aged normal specimens, and late-stage complement activation (C9) also tends to increase. This latter finding suggests that complement activation may contribute to loss of dopaminergic neurons in some individuals with PD. Complement activation on melanized neurons appears to decrease with normal aging, suggesting a possible neuroprotective role for this process in the normal substantia nigra.

Journal Article↗
PubMed1975

Consumption of classical complement components by heart subcellular membranes in vitro and in patients after acute myocardial infarction.

Experiments were conducted to characterize the antibody-independent activation of complement in human serum by isolated human heart mitochondrial membranes in vitro and to determine whether similar patterns of complement consumption occurred in patients after acute myocardial infarction. Direct evidence for the interaction of C1 and heart mitochondrial membranes was obtained by mitochondria-C1 binding and elution experiments. Exposure of normal human sera to isolated human heart mitochondria at 37 degrees C resulted in the consumption of C1, C4, C2, and C3 without significant consumption of the terminal components of the complement system (C6 through C9). The consumption occurred in the absence of detectable anti-heart mitochondria autoantibody, was demonstrated to be calcium dependent, and was inhibited by either 0.01 M EDTA or ethylene glycol bis(bets-aminoethyl ether) N,N,N',N',-tetraacetic acid (EDTA). Although specific absorption of C1q from human sera inhibited the mitochondria-dependent activation of C4, C3 donsumption was not affected. These data indicate that the consumption of C4 and C2 likely occurred due to the mitochondrial membrane-mediated activation of C1, but that the consumption of the C3 did not necessarily involve either the classical or alternative complement pathways. After the in vitro characterization of the mitochondria-dependent activation of the complement system, additional studies were performed to determine whether similar consumption occurred in patients after acute myocaridal infarction. During a 72-h period after hospital admission significant decreases in C1, C4, and C3 occurred in six patients with recent chest pain but no evidence of acute myocardial infarction. These studies suggest that myocardial cell necrosis results in the release of subcellular membrane constituents capable of activating the complement system in the absence of detectable anti-heart autoantibodies; such activation may be responsible in part for the development of acute inflammation and evolution of the infarct size following coronary artery occulusion.

Autoantibodies↗
PubMed1987

Ultrastructural localization of the membrane attack complex of complement in human renal tissues.

Utilizing a monoclonal antibody (Poly C9-MA) to a neoantigen of the C9 portion of the membrane attack complex of complement (MAC), immunoelectron (IEM) and immunofluorescent (IF) microscopy were performed on kidney tissue from normal humans and patients with insulin-dependent diabetes mellitus (IDDM) and type II membrano-proliferative glomerulonephritis (MPGN II). Comparative studies were conducted using polyclonal antibodies to human C3, C5, IgG, IgA, and IgM. In normal human tissue, there was a close correlation between increasing chronologic age and the quantity of MAC deposited in the mesangial stalk, along the interstitial aspect of and within tubular basement membranes (TBMs) and in arteriolar walls. IF of kidney tissues from 12 patients with IDDM with varying degrees of mesangial expansion and glomerulosclerosis demonstrated a direct relationship between the degree of tissue damage and the amount of MAC deposited in the mesangium. IEM of three normal and four diabetic specimens revealed reaction product of Poly C9-MA on linear and circular membranous structures within the mesangium, TBMs, and vessel walls, and within the glomerular basement membranes (GBMs) in diabetic subjects. Evidence is presented that these structures, which have been previously described by routine electron microscopy, represent cellular debris in these loci on which Poly C9-MA has been deposited. In MPGN II, Poly C9-MA and C3 were distributed within subepithelial deposits, along either side of the dense deposits (DDs) within the GBMs and TBMs, and around circular masses of DDs within the mesangium.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1983

Neoantigen of the polymerized ninth component of complement. Characterization of a monoclonal antibody and immunohistochemical localization in renal disease.

A monoclonal antibody to a neoantigen of the C9 portion of the membrane attack complex (MAC) of human complement has been developed and characterized. The distribution of this neoantigen was assessed by indirect immunofluorescence microscopy in nephritic and nonnephritic renal diseases. The antibody (Poly C9-MA) reacted on enzyme-linked immunosorbent assay (ELISA) with a determinant in complement-activated serum that was undetectable in normal human serum (NHS). Zymosan particles incubated in NHS had positive immunofluorescent staining with Poly C9-MA; however, binding of Poly C9-MA was not observed with zymosan particles incubated in sera deficient in individual complement components C3, C5, C6, C7, C8, or C9. Reconstitution of C9-deficient sera with purified C9 restored the fluorescence with Poly C9-MA. Poly C9-MA reacted positively by ELISA in a dose-dependent manner with purified MC5b-9 solubilized from membranes of antibody-coated sheep erythrocytes treated with NHS but not with intermediate complement complexes. Poly C9-MA also reacted in a dose-dependent manner on ELISA and in a radioimmunoassay with polymerized C9 (37 degrees C, 64 h) (poly C9) but not with monomeric C9. Increasing amounts of either unlabeled poly C9 or purified MC5b-9 inhibited the 125I-poly C9 RIA in an identical manner. These studies demonstrate that Poly C9-MA recognizes a neoantigen of C9 common to both the MAC and to poly C9. By immunofluorescence, Poly C9-MA reacted minimally with normal kidney tissue in juxtaglomerular loci, the mesangial stalk, and vessel walls. Poly C9-MA stained kidney tissue from patients with glomerulonephritis in a pattern similar to that seen with polyclonal anti-human C3. In tissue from patients with nonnephritic renal disease--diabetes, hypertension, and obstructive uropathy--Poly C9-MA was strongly reactive in the mesangial stalk and juxtaglomerular regions, tubular basement membranes, and vascular walls. Poly C9-MA binding was especially prominent in areas of advanced tissue injury. Poly C9-MA frequently stained loci where C3 was either minimally present or absent. These studies provide strong evidence for complement activation not only in nephritic but also in nonnephritic renal diseases.

Adult↗