Ba and Bb Fragments of Factor B Activation:
Fragment Production, Biological Activities, Neoepitope Expression and Quantitation in Clinical Samples

Kolb, William P.; Morrow, Phillip R.; Tamerius, John D.

doi:10.1159/000463093

Cited by 63 publications

(32 citation statements)

References 68 publications

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“…There is full activation of the classical complement pathway in plaque tissue, 11 and localization of the autolytic MAC on damaged transformed myocytes emphasizes the harmful aspects of this activation. In contrast, the failure to identify more than trace amounts of fraction Bb of factor B, a specific marker for activation of the alternative pathway, 29 in either normal artery or nearby plaque tissue would suggest that activation of the alternative pathway is not a significant factor.…”

Section: Discussionmentioning

confidence: 98%

Complement Components, but Not Complement Inhibitors, Are Upregulated in Atherosclerotic Plaques

Yasojima

Schwab²,

McGeer³

et al. 2001

ATVB

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Abstract-Complement activation occurs in atherosclerotic plaques. The capacity of arterial tissue to inhibit this activation through generation of the complement regulators C1 inhibitor, decay accelerating factor, membrane cofactor protein (CD46), C4 binding protein (C4BP), and protectin (CD59) was evaluated in pairs of aortic atherosclerotic plaques and nearby normal artery from 11 human postmortem specimens. All 22 samples produced mRNAs for each of these proteins. The ratios of plaque versus normal artery pairs was not significantly different from unity for any of these inhibitors. However, in plaques, the mRNAs for C1r and C1s, the substrates for the C1 inhibitor, were increased 2.35-and 4.96-fold, respectively, compared with normal artery; mRNA for C4, the target for C4BP, was elevated l.34-fold; and mRNAs for C7 and C8, the targets for CD59, were elevated 2.61-and 3.25-fold, respectively. By Western blotting and immunohistochemistry, fraction Bb of factor B, a marker of alternative pathway activation, was barely detectable in plaque and normal arterial tissue. These data indicate that it is primarily the classical, not the alternative pathway, that is activated in plaques and that key inhibitors are not upregulated to defend against this activation. (Arterioscler Thromb

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Section: Discussionmentioning

confidence: 98%

Complement Components, but Not Complement Inhibitors, Are Upregulated in Atherosclerotic Plaques

Yasojima

Schwab²,

McGeer³

et al. 2001

ATVB

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“…The study group consisted of 31 patients with AMI, 17 patients with unstable angina pectoris (UAP), 19 patients with stable angina pectoris (SAP), and 20 normal volunteers (Table 1). AMI was defined by at least two of the following: 1) angina lasting longer than 30 minutes, unrelieved by rest, 2) serum creatine kinase-MB fraction greater than 5%, 3) inversion or elevation of the ST-T waves, and 4) positive results from either the technetium 99m-pyrophosphate or thallium 201 scan.7-9 UAP was diagnosed according to American Heart Association criteria.…”

Section: Methodsmentioning

confidence: 99%

The complement system in ischemic heart disease.

et al. 1990

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The mechanisms by which tissue injury after acute myocardial infarction (AMI) occurs has not been fully elucidated. Recent evidence in experimental models has suggested involvement of the complement system in microvascular and macrovascular injury subsequent to AMI. With respect to angina pectoris, whether or not the complement system is activated is not clear. The present study assessed the role of complement as a mediator of myocardial inflammation by quantifying products of complement activation, including C3d, C4d, Bb, and SC5b-9 complexes, in 31 patients with AMI, 17 patients with unstable angina pectoris, 19 patients with stable angina pectoris, and 20 normal volunteers. The plasma C3d levels increased in patients with AMI and in those with unstable angina pectoris (p<0.01). The plasma levels of C4d, Bb, and SC5b-9 increased only in patients with AMI (p<90.01). The plasma SC5b-9 level was related to peak creatine phosphokinase (r=0.71) and inversely related to the ejection fraction (r= -0.71). The plasma SC5b-9 level of patients with congestive heart failure was higher than that of patients without congestive heart failure in AMI. These results show that activation of complement system occurs after AMI and show an association of myocardial damage with complement activation. With respect to angina pectoris, the complement system is mildly activated in patients with unstable angina pectoris; however, the cardiac function of patients with unstable angina pectoris is not damaged. The complement system of patients with stable angina pectoris is not activated. (Circulation 1990;81:156-163) R ecent studies in experimental models suggest that acute myocardial ischemia is associated with activation of the complement system. First, studies in the baboon have established that C3, C4, and C5 are deposited in most infarction myocardial fibers.12 Second, by inactivating the complement system in vivo with cobra venom factor, a significant reduction in myocardial damage was achieved in an animal model.3 Also, a few studies report the complement activation in vivo in patients with acute myocardial infarction (AMI).4-6 However, it is not clear whether the activated complement system affects the myocardial necrotic size and cardiac function in human myocardial infarction. It is also unknown whether or not the complement system is activated in patients with angina pectoris (AP). This study assessed complement activation in patients with AMI and AP by directly measuring by-products of the reaction. The degree of activation of the complement system was compared with the hemodynamic manifestations and peak creatine phosphokinase (CPK) in patients with AMI. MethodsThe study group consisted of 31 patients with AMI, 17 patients with unstable angina pectoris (UAP), 19 patients with stable angina pectoris (SAP), and 20 normal volunteers (Table 1). AMI was defined by at least two of the following: 1) angina lasting longer than 30 minutes, unrelieved by rest, 2) serum creatine kinase-MB fraction greater than 5%, 3) inversion or elev...

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“…This factor has been reported to be elevated in several tumors and thought to be induced by cytokines including interleukins and interferons (30)(31)(32)35,(36)(37)(38). Complement factor B (93 kDa) is cleaved by factor D into N-terminal Ba (30 kDa) and C-terminal Bb (63 kDa) fragments (33). The latter fragment was found to induce apoptosis, most likely through the effect on host immune response by complement factor Bderived fragment Bb in leukemia studies (39).…”

Section: Methods 1 Methods 2 Methods 3 ---------------------------------mentioning

confidence: 99%

“…Complement factor B (93 kDa) possesses non-glycosylated and glycosylated forms (30)(31)(32), and is cleaved by factor D into N-terminal Ba fragment (30 kDa) and C-terminal Bb fragments (63 kDa) (33). Low and high molecular weight bands of complement factor B in Patient lanes 1, 2, and 9 in Fig.…”

Section: ------------------------------------------------------------mentioning

confidence: 96%

Pre-analytic saliva processing affect proteomic results and biomarker screening of head and neck squamous carcinoma

et al. 2007

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Abstract. The objective of this study was to assess the effect of pre-analytical processing on proteomic analysis of saliva and to identify salivary biomarkers for potential clinical applications. Saliva samples from five healthy individuals and three head and neck squamous carcinoma (HNSC) patients were initially depleted of major protein constituents. Saliva from healthy subjects was divided and processed by three different methods prior to liquid chromatography and tandem mass spectrometry technique (LC-MS/MS) analysis. The results showed marked differences amongst the methods. The SDS-PAGE separation and in-gel digestion method yielded the highest number of proteins that included the majority of those identified by the other two methods. The in geldigestion method was used in the LC-MS/MS analysis of saliva from three HNSC patients and the results were compared with those from healthy subjects. Our analysis identified two proteins, ·-1-B-glycoprotein and complement factor B proteins, to be present in patients but not in normal specimens. Paradoxically, cystatin S, parotid secretory factor, and poly-4-hydrolase ß-subunit proteins were detected in most normal salivas but not in patient specimens. Subsequent analysis of complement factor B by Western blotting showed strong immunoreactive bands of complement factor B in HNSC patients' and negative or weakly positive in normal saliva samples. We conclude that: 1) initial saliva processing affects protein analysis, 2) in-gel digestion followed by LC-MS/MS detects the most saliva proteins, 3) certain proteins are differentially found in patient and normal salivas and 4) a small set of proteins can be targeted for future validation for clinical investigation. IntroductionSaliva is a readily accessible secretion that plays an important role in the maintenance of oral homeostasis, tooth integrity, initiation of digestion, and antimicrobial defense (1-3). Saliva is protein rich and may constitute a valuable source of diagnostic and therapeutic markers in head and neck squamous cell carcinoma (HNSC) patients (4-6). The major components of saliva are mucins, proline-rich glycoproteins, amylase, lipase and a variety of antimicrobial proteins and peptides that include agglutinin, cystatins, lisozyme, lactoferrin, immunoglobulins, histatins and defensins (7-17). Numerous less common proteins derived from either active salivary secretion or through plasma filtration have also been identified (18-21). Analysis of these proteins may provide important information in health and diseased states.It has recently been acknowledged that proteomic analysis reflects the net sum of the metabolic and functional states of cells and secretions from tissues (22). Advances in both technological and bioinformatic fields have led to a plethora of efforts to identify diagnostic, prognostic and therapeutic targets using human secretions and body fluids (4). However, major obstacles remain to complicate and impede the clinical implementation of this technology in human materials. These include sa...

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Ba and Bb Fragments of Factor B Activation: Fragment Production, Biological Activities, Neoepitope Expression and Quantitation in Clinical Samples

Cited by 63 publications

References 68 publications

Complement Components, but Not Complement Inhibitors, Are Upregulated in Atherosclerotic Plaques

Complement Components, but Not Complement Inhibitors, Are Upregulated in Atherosclerotic Plaques

The complement system in ischemic heart disease.

Pre-analytic saliva processing affect proteomic results and biomarker screening of head and neck squamous carcinoma

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