Biomedical subjects

F C de Beer

Publications and source records attributed to F C de Beer.

At least 37 records · Page 2Linked to original sources

PubMed1997

Alternative forms of the scavenger receptor BI (SR-BI).

The class B, type I scavenger receptor has been implicated as a receptor for high density lipoprotein (HDL). We have isolated a murine cDNA clone encoding an alternative form of SR-BI that differs in the putative cytoplasmic domain of the receptor. This variant form, likely the result of alternative mRNA splicing, is designated SR-BI.2. SR-BI.2 mRNA was detected in mouse tissues known to express SR-BI and tissue-specific differences in the relative abundance of SR-BI.2 were apparent. In mouse adrenal glands, SR-BI.2 represented approximately one-third of total SR-BI mRNA, whereas in mouse testes, SR-BI.2 represented the major mRNA species (79% of total). SR-BI.2 was also detected in the human cell lines examined, namely HeLa, HepG2, and THP-1 cells. CHO cells transfected with the mouse SR-BI.2 cDNA expressed significant levels of SR-BI.2 protein and acquired the ability to take up fluorescent lipid (DiI) from DiI-HDL. Alternative splicing of SR-BI represents a potentially important process for the regulation of SR-BI expression and function.

Adipose Tissue↗

PubMed1997

Adenoviral vector-mediated overexpression of serum amyloid A in apoA-I-deficient mice.

Serum amyloid A (SAA) is an acute phase reactant that can become the predominant apolipoprotein of high density lipoprotein (HDL) during severe inflammatory states. However, the function of SAA is unknown. To study the ability of SAA to form HDL in the absence of apolipoprotein A-I, we expressed the mouse SAA pI 6.15 (CE/J) isoform in apolipoprotein A-I knock-out (apoA-I (-/-)) mice using a recombinant adenovirus. As a control, apoA-I (-/-) mice were injected with an adenovirus expressing human apoA-I. High level expression of plasma SAA was obtained in the absence of any endogenous acute phase SAA production. SAA expression increased plasma HDL cholesterol levels about 2-fold, but to a lesser extent than the expression of apoA-I (about 10-fold). The HDL particles isolated by density ultracentrifugation from SAA-expressing mice were heterogeneous in size and composition and rich in free cholesterol as well as apoE and apoA-IV. Of the SAA expressed in the plasma, only a small fraction (4%) was associated with HDL particles in contrast to expressed apoA-I, of which 62% was associated with HDL. We conclude that SAA is unable to substitute for apoA-I in HDL particle formation.

Acute-Phase Reaction↗

PubMed1997

Secretory non-pancreatic phospholipase A2: influence on lipoprotein metabolism.

Lipoprotein metabolism is markedly altered during inflammation. The concentration of human secretory phospholipase A2 (sPLA2) can increase hundreds of fold in inflammatory fluids and in the circulation. It was detected in atherosclerotic lesions where many inflammatory genes are induced. As sPLA2 has been reported to act on lipoproteins as substrates, lipoprotein profiles in transgenic mice expressing sPLA2 were studied. HDL levels were markedly decreased in transgenic mice overexpressing sPLA2. HDL in the transgenics were smaller in size, with a significant decrease (11%) in phospholipid content compared to nontransgenic littermates. In sPLA2 transgenic mice and transgenic mice expressing both sPLA2 and human apolipoprotein B (apoB), the concentrations of apoB-containing lipoproteins were not altered. We conclude that sPLA2 alters HDL metabolism and could be responsible for the depressed levels of HDL that exist during chronic inflammatory diseases.

Animals↗

PubMed1996

Structure of the mouse Saa4 gene and its linkage to the serum amyloid A gene family.

The serum amyloid A (SAA) proteins are a polymorphic family of apolipoproteins associated with high-density lipoproteins (HDL). Three distinct subfamilies have been identified: (i) a cytokine-induced acute phase subfamily that is hepatically produced and can become the major apolipoprotein on HDL (SAA1, SAA2); (ii) a peripherally produced acute phase SAA3 that is only a minor HDL apolipoprotein; and (iii) a constitutive subfamily (SAA4) that is a minor normal HDL apolipoprotein comprising more than 90% of the SAA during homeostasis. Here we define the structure of the Saa4 gene. Similar to other Saa family members, it has four exons and three introns. It is 4588 bp long from the transcription start site to the end of the 3'-untranslated region and is approximately 20% larger than other Saa genes. We have located Saa4 11 kb upstream from Saa3 and 5 kb downstream from Saa1, with the pseudogene approximately 1 kb from the 5' end of Saa4. Saa4 has the same orientation as most other Saa family members, with only Saa2 having an opposing orientation. These data promote our understanding of the evolution of the Saa family. They enhance our ability to develop the mouse as a transgenic and gene deletion model to advance the understanding of the function of these apolipoproteins.

Animals↗

PubMed1996

Amino terminal region of acute phase, but not constitutive, serum amyloid A (apoSAA) specifically binds and transports cholesterol into aortic smooth muscle and HepG2 cells.

The human apoSAA proteins comprise both acute phase (apoSAA1, apoSAA2) and constitutive (apoSAA4) isoforms; all are expressed in human atherosclerotic lesions as well as in liver. Recombinant acute phase apoSAA binds cholesterol with an affinity of approximately 170 nM and enhances cholesterol uptake by HepG2 cells (J. Lipid Res. 1995. 36:37-46). In the present study, we sought to define the region of acute phase apoSAA involved in cholesterol binding and to investigate the ability of constitutive apoSAA4 to bind cholesterol. Binding of [3H]cholesterol to apoSAAp was inhibited by unlabeled cholesterol (1-100 nM), but not significantly by vitamin D and estradiol. Direct binding of acute phase, but not constitutive, apoSAA to the surfaces of polystyrene microtiter wells was strongly diminished in the presence of cholesterol. The ability of apoSAAp to bind cholesterol was inhibited by antibodies to human apoSAA1 and to peptide 1-18 of apoSAA1. There was only slight inhibition of cholesterol binding by antibodies to peptide 40-63, and no inhibition by antibodies to peptides spanning regions containing amino acid residues 14-44 and 59-104. [3H]cholesterol uptake by neonatal rabbit aortic smooth muscle and HepG2 cells was enhanced by a synthetic peptide corresponding to amino acids 1-18 of hSAA1, but not by peptides corresponding to amino acids 1-18 of hSAA4. [3H]cholesterol uptake by HepG2 cells was slightly increased by a peptide corresponding to amino acids 40-63 of hSAA1. These findings suggest that apoSAA modulates the local flux of cholesterol between cells and lipoproteins during inflammation and atherosclerosis.

Amino Acid Sequence↗

PubMed1995

Serum amyloid A protein enhances the activity of secretory non-pancreatic phospholipase A2.

The acute-phase proteins serum amyloid A protein (SAA) and secretory phospholipase A2 (sPLA2) are simultaneously expressed during inflammatory conditions. SAA associates with high-density lipoprotein (HDL) altering its physicochemical composition. We found that purified acute-phase SAA, but not the constitutive form, markedly enhances the lipolytic activity of sPLA2 in a dose-related manner with phosphatidylcholine/lysophosphatidylcholine or phosphatidylethanolamine/lysophosphatidylethanolamine liposomal substrates. Normal HDL was found to reduce activity of sPLA2 in a dose-dependent manner, but when acute-phase HDL containing 27% SAA was tested, it enhanced sPLA2 activity. Immunopurified monospecific antibodies against SAA completely abolished the enhancing activity of SAA and acute-phase HDL. Given the central role of HDL in lipoprotein metabolism, the interaction between HDL, SAA and sPLA2 may account for changes detected in lipoprotein metabolism during the acute phase.

Acute-Phase Proteins↗

PubMed1995

Anti-inflammatory HDL becomes pro-inflammatory during the acute phase response. Loss of protective effect of HDL against LDL oxidation in aortic wall cell cocultures.

We previously reported that high density lipoprotein (HDL) protects against the oxidative modification of low density lipoprotein (LDL) induced by artery wall cells causing these cells to produce pro-inflammatory molecules. We also reported that enzyme systems associated with HDL were responsible for this anti-inflammatory property of HDL. We now report studies comparing HDL before and during an acute phase response (APR) in both humans and a croton oil rabbit model. In rabbits, from the onset of APR the protective effect of HDL progressively decreased and was completely lost by day three. As serum amyloid A (SAA) levels in acute phase HDL (AP-HDL) increased, apo A-I levels decreased 73%. Concomitantly, paraoxonase (PON) and platelet activating factor acetylhydrolase (PAF-AH) levels in HDL declined 71 and 90%, respectively, from days one to three. After day three, there was some recovery of the protective effect of HDL. AP-HDL from human patients and rabbits but not normal or control HDL (C-HDL) exhibited increases in ceruloplasmin (CP). This increase in CP was not seen in acute phase VLDL or LDL. C-HDL incubated with purified CP and re-isolated (CP-HDL), lost its ability to inhibit LDL oxidation. Northern blot analyses demonstrated enhanced expression of MCP-1 in coculture cells treated with AP-HDL and CP-HDL compared to C-HDL. Enrichment of human AP-HDL with purified PON or PAF-AH rendered AP-HDL protective against LDL modification. We conclude that under basal conditions HDL serves an anti-inflammatory role but during APR displacement and/or exchange of proteins associated with HDL results in a pro-inflammatory molecule.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

PubMed1995

Association of apolipoprotein E with murine amyloid A protein amyloid.

BACKGROUND: Experimental amyloid A protein (AA) amyloidosis in mice is the most rapid type of amyloid formed, thus providing a valuable model to study amyloid formation. Recent studies have suggested the importance of apolipoprotein E (apoE) in Alzheimer's disease and systemic amyloidoses. To help understand the role of apoE in amyloidoses, we examined amyloid tissue for the presence of apoE in mouse AA amyloid. EXPERIMENTAL DESIGN: Mice were injected with amyloid-enhancing factor and silver nitrate to induce amyloid deposition. Spleens were examined for Congo red staining and serum amyloid A, serum amyloid P component, and apoE immunostaining. In addition, RNA analysis was performed to measure the expression of apoE in various tissues after amyloid induction. RESULTS: We have found that apoE is associated with mouse amyloid. Ab to apoE consistently detected the presence of increased levels of apoE in amyloid tissue. Immunohistochemical analyses confirmed that the apoE immunoreactivity co-associated with AA and serum amyloid P in the amyloid fibrils. Northern blot analysis of amyloid tissue showed an increase in apoE messenger RNA compared with control tissue. CONCLUSIONS: This is the first demonstration of apoE in mouse amyloid tissue. The data presented here, along with previous studies, suggest that apoE may be involved in amyloidogenesis. These studies validate the mouse model for studying the role of apoE in amyloid fibrillogenesis. The use of transgenic and gene-inactivated mice will help to elucidate the role and mechanism of apoE in amyloid formation.

Amyloidosis↗

PubMed1995

Serum amyloid A (SAA): influence on HDL-mediated cellular cholesterol efflux.

Normal high density lipoprotein (N-HDL) is remodeled during acute phase (AP) reactions by the association of serum amyloid A (SAA) and the depletion of apolipoprotein (apo) A-I. To determine the impact of this remodeling on HDL function, the capacities of N-HDL and AP-HDL to associate with and promote cholesterol efflux from human monocytic THP-1 cells were compared. THP-1 cells preferentially bound AP-HDL compared with N-HDL. Examination of the AP-HDL particles bound to THP-1 cells revealed a disproportionate association of an apoSAA-enriched, apoA-I-depleted subpopulation compared with the composition of the starting material. However, N-HDL and AP-HDL promoted cholesterol efflux from THP-1 cells equally efficiently and in a dose-dependent manner. When N-HDL was experimentally remodeled with apoSAA to achieve an apoprotein composition similar to that of the preferentially bound particles, cellular cholesterol efflux was reduced by 30%. The remodelling of HDL with apoSAA during the acute phase reaction alters cholesterol efflux only when apoSAA constitutes more than 50% of the HDL protein.

Apolipoprotein A-I↗

PubMed1995

Characterization of constitutive human serum amyloid A protein (SAA4) as an apolipoprotein.

Serum amyloid A proteins (SAAs), a family of homologous molecules, are apolipoproteins of high density lipoprotein (HDL). They can be divided into two groups. The first group comprises the well-characterized acute phase SAAs that associate with HDL during inflammation, thereby remodeling the HDL particle by displacing apolipoprotein (apo)A-I. The second group consists of the recently discovered constitutive SAAs, mouse SAA5 and human SAA4. They exist as minor apolipoproteins on HDL but constitute more than 90% of the total SAA during homeostasis. We have characterized human SAA4 as an apolipoprotein. During homeostasis, SAA4 is synthesized only in the liver. Purification of SAA4 has been described and its plasma concentration has been established at 55 +/- 13 micrograms/ml in 26 healthy individuals. It was present on all HDL density classes and very low density lipoprotein (VLDL) but was absent from low density lipoprotein (LDL). Using two-dimensional electrophoresis and phosphorimaging, SAA4 was found to be associated with a specific subpopulation of only three HDL particles, not involved in the initial cholesterol transfer from cells.

Acute-Phase Reaction↗

PubMed1994

Mouse serum amyloid A protein (SAA5) structure and expression.

A novel member of the mouse serum amyloid A protein family, SAA5, has been identified as a normal apolipoprotein component of non-acute-phase high density lipoprotein (HDL). The structure of SAA5 was derived from a clone isolated from a normal Balb/c liver cDNA library. The clone predicts a pre-SAA5 molecule of 130 residues from which an 18-residue leader peptide is cleaved. The mature molecule has an octapeptide insert spanning from position 70 to 77. Similar inserts are found in human C-SAA and, paradoxically, in acute-phase SAA molecules of a number of other species. There is 48% amino acid identity between apo-SAA5 and the other mouse SAA proteins and 57% identity between the human C-SAA and apo-SAA5. The SAA5 mRNA is three times larger than previously identified SAA mRNAs. Although SAA5 is constitutively expressed in the liver, it has a rapid albeit muted response to inflammatory stimuli. The increase of SAA5 mRNA is due to increased transcription rather than mRNA stabilization. Plasma SAA5 levels during the acute phase are biphasic, either because of translational control or displacement from HDL and rapid clearance. We propose that constitutive SAAs (SAA5) on normal HDL contribute to its normal physiological role, whereas the dramatically inducible family members (SAA1, SAA2, SAA3) equip this particle for an altered functional role during inflammation.

Amino Acid Sequence↗

PubMed1994

Serum amyloid A protein family. Differential induction by oxidized lipids in mouse strains.

During inflammation, serum amyloid A (SAA) protein increases up to 1000-fold and can become a major component of high-density lipoprotein (HDL). We have identified a new apolipoprotein molecule (SAA5) as a distinct member of the SAA family. It differs from the inflammatory isotypes (SAA1, SAA2, and SAA3) not only in structure but in the fact that it is constitutive on normal HDL where it accounts for more than 90% of total SAA. Whereas all members of the SAA family, including SAA5, responded to endotoxin administration, SAA5 contrasted with other SAAs in its resistance to induction either by a high-fat, high-cholesterol atherogenic diet or the injection of mildly oxidized LDL (MM-LDL). These data provide further evidence that the induction of inflammatory molecules by oxidized lipids is selective. In atherosclerosis-susceptible C57BL/6 mice and atherosclerosis-resistant C3H/HeJ mice, the inflammatory SAA isotypes (SAA1, SAA2, and SAA3) responded in a strain-specific manner to oxidized lipids either generated with feeding of the atherogenic diet or introduced by MM-LDL injection. We hypothesize that the constitutive SAA5 molecules on normal HDL may contribute to its normal physiological role and that the dramatic induction of the inflammatory SAA subfamily equips the particle for an altered yet related functional role appropriate to the inflammatory state.

Animals↗

PubMed1993

Structural prerequisites for serum amyloid A fibril formation.

Most studies of experimental amyloid A protein (AA) amyloidosis in mice have been performed in type A mice with BALB/c as the prototype. In these mice the products of two genes, SAA1 and SAA2, are the major apo-SAA isoforms on high density lipoprotein (HDL). Of these two isoforms, that differ at nine amino acids, only apo-SAA2 is rapidly cleared and deposited as amyloid fibrils. No mouse strain has ever been shown to be completely resistant to amyloid induction. We have found the CE/J mouse strain to be exceedingly resistant to amyloidogenesis. Data indicate that this resistance is not due to a lack of apo-SAA synthesis but rather resides in the unique apo-SAA isoform in this strain. CE/J mice have a single major apo-SAA isoform (pI 6.15) the product of a single gene. This is a hybrid molecule with features of both apo-SAA1 and apo-SAA2, differing from the latter at only six amino acids. When CD studies were performed to explore the structural relationship of this isoform to apo-SAA1 and apo-SAA2, we found that when bound to heparan sulfate proteoglycan the CE/J pI 6.15 isoform fails to undergo the beta-sheet folding typical for apo-SAA2. This evidence suggests that the folding effect of heparan sulfate proteoglycan on apo-SAA2 is important in amyloid formation.

Amino Acid Sequence↗

PubMed1993

Syrian and Armenian hamsters differ in serum amyloid A gene expression. Identification of novel Syrian hamster serum amyloid A subtypes.

Amyloid A (AA) amyloidosis is widespread throughout the animal kingdom. Several factors including: 1) precursor production; 2) precursor structure; 3) precursor degradation; and 4) precursor/product interaction with the pentraxin serum amyloid P have been implicated in amyloidogenesis, but the exact sequence of events leading to AA fibril formation and deposition remains unclear. Most models of experimental amyloidosis, including golden Syrian hamsters (Mesocricetus auratus), involve massive and repeated inflammatory stimulation; however, the model of spontaneous amyloidosis with aging in female, but not male, Syrian hamsters permits analysis of amyloidogenic factors in the absence of inflammation. Another genus, the Armenian hamster (Cricetulus migratorius), differs from Syrian hamsters both in gender-specific serum amyloid P expression and susceptibility to AA amyloidosis. In this study, we describe novel SAA molecules in the Syrian hamster in the presence and absence of inflammation. We demonstrate that, based on isoelectric separation, the Syrian hamster SAA proteins can be separated into two broad subfamilies. Plasma SAA concentration in female Syrian hamsters increases spontaneously with age, and fragments of a basic SAA isotype expressed both hepatically and extrahepatically are selectively deposited as AA fibrils. After inflammatory stimulation, the patterns of SAA gene expression in Syrian and Armenian hamsters differ. In Syrian hamsters, both hepatic SAA mRNA and the high density lipoprotein apoSAA content increase approximately 1000-fold; in Armenian hamsters, hepatic SAA mRNA is limited in quantity and different in structure; and although plasma SAA proteins increase three- to fivefold, apoSAA is not detectable in high density lipoprotein. The results suggest that regulation and site of precursor production as well as precursor structure influence AA amyloidogenesis in these two hamster genera.

Amino Acid Sequence↗

PubMed1993

Characterization of the inbred CE/J mouse strain as amyloid resistant.

Inbred CE/J mice have been identified as extremely resistant to azocasein-induced amyloidosis relative to five commonly used inbred strains, A/J, CBA/J, C57BL/6J, C3H/HeN, and SJL/J. The enhanced amyloid resistance in CE/J mice seems to derive from the novel structure of the SAA gene family in CE/J mice, as determined by Southern blot hybridization analysis of SAA gene structure and isoelectric focusing analysis of acute phase SAA proteins in the six inbred strains. In CE/J mice, a single, novel SAA isoform of pI 6.15 is present, whereas in the other strains the amyloidogenic SAA2 isoform (pI 6.3) is codominantly expressed with SAA1 (pI 6.45). Two other inbred strains, PERU and IS/CAM, share common SAA specific HindIII DNA fragments with CE/J mice. Wild-derived Mus musculus mice differ from all of the inbred strains studied, both in SAA gene structure and in the pattern of SAA isoform production; two isoforms, one pI 6.15 and the other pI 6.3 (corresponding to SAA2), were codominantly expressed. Only the pI 6.15 isoform, not SAA1 and 2, was produced by CE/J mice in response to lipopolysaccharide, casein, silver nitrate, interleukin-1, or tumor necrosis factor; tumor necrosis factor was a weaker stimulus than interleukin-1 for the pI 6.15 isoform as it is for SAA1 and 2 production in the other inbred strains. This study provides a new line of evidence supporting the role of precursor structure as a determining factor in murine amyloid A amyloidosis and provides a valuable model for studies of amyloidogenesis.

Acute-Phase Reaction↗

PubMed1992

Mouse serum amyloid A protein. Complete amino acid sequence and mRNA analysis of a new isoform.

Four serum amyloid A protein (SAA) genes and two gene products, apo-SAA1 and apo-SAA2 were identified in BALB/c mice (type A). SJL/J mice (type B) are thought to be defective in apo-SAA2 expression. A unique variant of mouse apo-SAA was identified in SJL/J mice by isoelectric-focusing analysis of high-density lipoprotein from endotoxin-treated mice. Complete amino-acid-sequence analysis of this quantitatively major form of SJL/J apo-SAA (pI 5.9) showed it to be identical with the apo-SAA2 isoform from BALB/c mice, except for the substitution of aspartic acid for alanine at position 101. Isoform-specific analysis of mRNA from liver of BALB/c and SJL/J mice and their F1 hybrid progeny (CSJLF1/J) mice revealed further differences in the 3' untranslated regions of the genes, not only encoding apo-SAA2 and apo-SAA pI 5.9, but also apo-SAA1. The SAA genes of SJL/J mice thus differ from BALB/c in exon 4. Additional minor isoforms corresponding to apo-SAA2 (pI 6.3) in SJL/J mice and apo-SAA (pI 5.9) in BALB/c mice were identified. We propose that, when analysing a multigene family such as SAA, thorough analysis at the protein level should complement molecular-biological approaches where the use of a too-limited repertoire of probes can obscure complexities.

Amino Acid Sequence↗

PubMed1992

Identification of novel members of the serum amyloid A protein superfamily as constitutive apolipoproteins of high density lipoprotein.

A novel serum amyloid A protein (SAA) has been identified as a normal apolipoprotein component of non-acute phase high density lipoprotein. This novel SAA has been designated "constitutive" SAA (C-SAA) to distinguish it from "acute phase" SAA (A-SAA). C-SAA was partially sequenced, and immunochemical analyses indicated that it constitutes a distinct subclass of apolipoproteins within the SAA superfamily. A C-SAA cDNA clone was isolated from a human liver library and sequenced. The clone predicts a pre-C-SAA molecule of 130 residues from which an 18-residue leader peptide is cleaved. The 112-residue mature molecule is 8 residues longer than human A-SAA; the size difference is due to the presence of an octapeptide between positions 70 and 77 that is not found in the corresponding region of human A-SAA. Paradoxically, octapeptides of similar composition are found at similar positions in the A-SAAs of a number of other species. The C-SAA octapeptide specifies the first two residues of a NSS tripeptide, the only potential N-linked glycosylation site in the molecule. Studies indicate that approximately 50% of these sites are glycosylated, thereby giving rise to two size classes, 14 and 19 kDa, of C-SAA in vivo. Human acute phase liver contains little C-SAA mRNA relative to the levels of A-SAA mRNA, and the treatment of PLC/PRF/5 hepatoma cells with monocyte-conditioned medium does not induce C-SAA mRNA concentrations to detectable levels, in contrast to the massive induction of A-SAA mRNA observed. C-SAA is therefore not a major acute phase reactant.

Amino Acid Sequence↗

PubMed1992

Localization of sequence-determined neoepitopes and neutrophil digestion fragments of C-reactive protein utilizing monoclonal antibodies and synthetic peptides.

We recently described 17 anti-CRP mAb, seven to native- (or conformational) and 10 to neo- (or sequence-determined) epitopes, including several anti-neo-CRP mAb specific for CRP peptide 199-206. In the present study, four new anti-native- and four new anti-neo-CRP mAb were generated and characterized by ELISA reactivity with native and modified human and rabbit CRP, as well as binding to pronase fragments of human CRP in Western blots. Assays with 17 synthetic CRP peptides identified anti-neo-CRP mAb specific for peptides 1-16, 14-24 and 137-152, respectively. The anti-neo-CRP mAb were reacted with fragments obtained by digesting CRP with multiple additional enzymes, including Staphylococcal V8 protease, trypsin, elastase, plasmin, thrombin and alpha-chymotrypsin. Native CRP was remarkably resistant to enzymic digestion, particularly in the presence of calcium, but was readily cleavable upon denaturation. Twenty-three informative fragments served to further distinguish mAb reactivity with at least four additional neo-CRP epitopes, which presumptively included residues in the regions of amino acids 22-45, 41-61, 114-121 and 130-138, respectively. The eight epitopes identified corresponded well with predicted regions of CRP antigenicity. In addition, at least six distinct native or conformation-determined epitopes were delineated. Reactivity of the anti-neo-CRP mAb with fragments of CRP generated by PMN enzymes indicated that regions sensitive to cleavage by neutrophil enzymes are located at approximately 3, 10 and 16 kD from the amino terminus of the CRP subunit. We expect that the anti-CRP mAb described and mapped herein will be useful tools for the elucidation of CRP structure and function.

Antibodies, Monoclonal↗