Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “PROPERDIN”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 235 records · Page 13Linked to original sources
PubMed1973

Hypocomplementemia of membranoproliferative nephritis. Dependence of the nephritic factor reaction on properdin factor B.

Membranoproliferative nephritis in children is frequently associated with a hypocomplementemia produced at least in part by C3 breakdown mediated by a circulating anticomplementary factor known as C3 nephritic factor (C3NeF). C3 breakdown by this factor in vitro requires the presence of a pseudoglobulin cofactor and magnesium. The present study provides evidence that properdin factor B (C3 proactivator) is activated in the nephritic factor reaction and is the direct mediator of C3 breakdown by C3NeF. Depletion of factor B from mixtures of normal human serum (NHS) and plasma from a patient with membranoproliferative nephritis (MPP), either by heating or by immune equivalence absorption, blocks C3 breakdown by C3NeF. Addition of purified factor B to these mixtures restores the anticomplementary effect. When purified factor B is added to mixtures of MPP and purified C3, breakdown also occurs. Associated with the C3 breakdown is a change in the electrophoretic mobility of factor B from the beta to the gamma position, a shift which has been associated with cleavage activation of the molecule. Further, serum factor B levels are often low in patients with membranoproliferative nephritis and bear a rough inverse correlation with C3NeF levels. It thus appears that factor B is the previously described heat-labile C3NeF cofactor. Whether the C3NeF reaction proceeds via a pathway comparable to that activated by the cobra venom factor or via that activated by zymosan or inulin cannot be determined from the present data.

Absorption↗
PubMed1983

Fulminant meningococcal infections in a family with inherited deficiency of properdin.

Three males in a large kindred died of meningococcal infections. In the index patient, properdin (P) was not detectable in serum. Two healthy males with a selective P deficiency were found in the family. There was no general susceptibility to infections, nor to other diseases as suggested by the family history. The serum bactericidal activity for Neisseria meningitidis group C, isolated from the index patient, was moderately reduced in P deficient serum, and was improved by addition of purified P.

Adolescent↗
PubMed1975

Genetic polymorphism of properdin factor B in the rhesus: evidence for single subunit structure in primates.

Properdin Factor B shows genetic polymorphism in the human and the polymorphic patterns in agarose gel electrophoresis suggest a tetrameric structure. Factor B polymorphism in the rhesus monkey has been demonstrated in the present study to be genetically determined and under the control of a single autosomal locus, rhesus Bf. Six codominant alleles, Bf-F, Bf-G-1, Bf-G-2, Bf-S-1, Bf-S-2 have been recognized and the first five have been shown to have gene frequencies of 0.307,0.160,0.016,0.377, and 0.139. The electrophoretic appearance of the polymorphic patterns does not suggest a tetrameric structure in the rhesus. Structural studies show purified human factor B to exist as a single subunit of molecular weight 94,000 daltons so that a tetrameric structure appears highly unlikely.

Animals↗
PubMed1975

Formation and composition of the C3 activating enzyme complex of the properdin system. Sequential assembly of its components on solid-phase trypsin-agarose.

An active C3 cleaving enzyme is generated when properdin factor B (glycine-rich beta-glycoprotein, GBG) is activated (GBG is cleaved) by factor D in the presence of C3b and Mg++. Factor D can be replaced by trypsin in this reaction but even then C3b and Mg++ are required. In the absence of C3b and/or Mg++ trypsin does not generate C3 cleaving activity from GBG although it cleaves GBG and releases its GGG fragment (B) under these conditions as well. Addition of C3b to GGG immediately after its release does not yield a C3 cleaving enzyme. These findings indicate that C3b, GBG and Mg++ interact, and that only in association with C3b can GBG be cleaved in a way that its enzyme activity, residing in a C3b, GGG complex, is expressed. The complex is labile (half-life at 20 degrees C: 9 minutes); Mg++ does not affect its stability nor is it essential for the activity. It was possible to sequentially fix on agarose the essential components of the C3 cleaving enzyme and thus to elucidate the single steps and the order of its formation. C3 was activated and the resulting C3b fragment fixed on agarose by incubating C3 with trypsin covalently bound to the agarose. The agarose-C3b intermediate was capable of binding GBG provided Mg++ was present. GBG could then be cleaved by factor D or trypsin added in solution; the solid-phase-fixed complex obtained had C3 cleaving activity, in the presence as well as absence of Mg++. Omission of any of these steps or components, or changes in the sequence did not give rise to an active enzyme. Mixtures of C3b, GBG and Mg++ have weak C3 cleaving activity by themselves. C3 cleavage in such incubation mixtures proceeds slowly for hours and is not accompanied by cleavage of GBG. There is thus complete analogy between the CVF-dependent and C3b-dependent C3 cleaving systems. C3b and CVF act in the same way, they form a reversible, weakly active C3 cleaving complex with GBG and Mg++, the activity of which is markedly enhanced but becomes subject to decay when GBG is cleaved by trypsin-like enzymes while bound to CVF or C3b.

Animals↗
PubMed1975

Properdin factor B (glycine-rich beta-glycoprotein or C3 proactivator)-polymorphism: genetic and biochemical aspects. First application to paternity cases.

Determination of genetic properdin factor B(Bf) polymorphism was carried out in immunofixation electrophoresis. Genetics of factor B were also studied after ageing, conversion with cobra venom and neuraminidase. In population studies the distribution of factor B in a West German population of 1245 non-related individuals was found to be: Bf F 2.73%, Bf FS 28.43%, Bf S 65.38%. Rare phenotypes (F 1F,F 1S, FS 1, SS 1) were seen in 3.46%. In addition a new variant, designated F1.6S, was observed. The application of factor B polymorphism to 68 paternity cases is discussed.

Aging↗
PubMed1989

Biosynthesis of properdin.

Properdin (P) is synthesized by the human promyelocytic cell line, HL-60, after differentiation with DMSO. The secreted P was physiochemically indistinguishable from purified plasma P. It was polymerized and able to bind to C3IBb-Sepharose but not to C3i-Sepharose. No extracellular precursor was present. The intracellular form, detected between 1 and 4 h after labeling, was similar but had a slightly lower Mr. It also bound reversibly to C3iBb-Sepharose, and polymers could be demonstrated by cross-linking. Pulse-chase experiments suggested the existence of an earlier, but undetectable, intracellular precursor(s). This form could not be immunoprecipitated even when harsh solubilization conditions and/or antibodies against reduced and denatured P were utilized. Studies with endoglycosidases F and H and tunicamycin indicated that the detectable intracellular precursor contains high mannose N-linked carbohydrate that is processed to the complex form before secretion. The sugars are not required for polymerization, secretion, or functional activity, or responsible for the electrophoretic heterogeneity. Polymerization of P is therefore an early intracellular event, perhaps carefully controlled to prevent anomalous aggregation.

Carbohydrate Conformation↗
PubMed1988

A 34-amino acid peptide of the third component of complement mediates properdin binding.

In this study, a peptide of 34 amino acids from the Mr 40,000 C terminus alpha-chain fragment of C3 was found to mediate properdin (P) binding. Treatment of the Mr 40,000 fragment with CNBr generated one major Mr 17,000 fragment that was capable of binding P. Amino acid sequence data placed the Mr 17,000 fragment within residues 1385 to 1540 of the C3 sequence. After analyzing this sequence for highly conserved segments within the C3 from other species (which bind P) and segments of low similarity within human C4, mouse C5, and alpha 2-macroglobulin (which do not bind P), a 34-amino acid (1402 to 1435) peptide was synthesized. This synthetic peptide bound to P and inhibited its binding to C3b. In addition, it exhibited negative regulatory activity on the alternative pathway as it inhibited the lysis of rabbit erythrocytes by normal human serum. These results show that the P-binding site is located within the residues 1402 to 1435 of the C3 sequence.

Amino Acid Sequence↗
PubMed1977

Interaction of zymosan and of activated properdin with factor D-depleted guinea pig serum: implications for the mechanism of initial C3 cleavage via the alternative complement pathway.

Factor D of the alternative C pathway was specifically removed from guinea pig serum. The resulting serum reagent (RD) supported neither the formation of a C3-cleaving enzyme on zymosan (Z) nor the inactivation of C3 or of factor B in the presence of Z or activated properdin (P). Addition of purified D to RD restored these properties. Studies were limited amounts of purified D were added to RD with Z or P as activating substances, gave the following results: (1) Inactivation of B and of C3 occurs in the presence of minute amounts of D. (2) C3 inactivation is more efficient than B inactivation and proceeds even in the absence of detectable enzymatic B activation. (3) C3 cleavage at any D concentration tested is always accompanied by uptake of C3 fragments onto Z. With respect to initial C3 cleavage via the alternative C pathway these data suggest that the initiating reaction is D-dependent, very efficient in depositing C3 fragments on particulate activating substances such as Z and able to utilize factor B in an apparently uncleaved form.

Animals↗
PubMed1976

Effect of proteolytic digestion on the structure and function of human properdin.

Human properdin (P) was found to be sensitive to the action of trypsin, chymotrypsin, pepsin, and Streptomycetes caesipitosus protease. Incubation of P with these enzymes resulted in loss of its functional activity and the production of antigenically deficient components compared to untreated P. Upon incubation with trypin, P was initially cleaved into a minor fragment and a major fragment. Further degradation ot the fragments occurred with prolongation of inculation time. The minor fragment was highly susceptible to further proteolysis compared to the major fragment which contained the carbohydrate moiety of the molecule. SDS-polyacrylamide gel electrophoretic analysis of trypsin-digested P suggested that the subunit polypeptide chains were initially cleaved at similar points to produce the major and minor fragments. The sedimentation velocity of the major fragment was higher than that of the intact molecule. The implications of these observations of the configuration of P are discussed.

Bacterial Proteins↗
PubMed1977

[Properdin and the protein composition of lymph and blood following resuscitation].

It was shown in experiments on dogs that the terminal blood letting with the subsequent reanimation by intrabone autoblood force pumping caused regular redistribution of proteins between blood, lymph, and tissues. Properdine and alpha-globulin retention in interstitium not eliminable by reanimation measures, and also stress secretion of gamma-globulins from the lymph nodes was noted.

Alpha-Globulins↗
PubMed1982

Properdin deficiency in a family with fulminant meningococcal infections.

Three males in a large family showed a selective deficiency of properdin (P). One of the P deficient individuals died from a fulminant infection with Neisseria meningitidis group C. The family history revealed three previous cases of similar infections with a fatal outcome. The deficiency did not appear to be associated with repeated bacterial infections. The pattern of inheritance suggested an X-linked mode of transmittance. However, heterozygous carriers were not clearly distinguished in the family. P deficient serum supported immune haemolysis in a normal fashion. Alternative pathway functions, such as the activation of C3 by inulin or zymosan, lysis of guinea-pig erythrocytes in agarose gel and opsonization of endotoxin coated oil particles, were grossly impaired in P deficient serum while efficient C3 activation was produced by addition of cobra venom factor.

Adolescent↗
PubMed1995

Fluorescent detection of microsatellite polymorphisms: properdin deficiency linked to PFC microsatellite.

Microsatellite polymorphisms are widely used to map the genes responsible for inherited disorders. The most commonly used detection is based on radioactive labelling and autoradiography. We now present the successful detection of fluorescence-labelled allelic fragments on an automated DNA sequencer. This allows for safer and quicker detection as well as a potential for more efficient processing of the data, e.g. for linkage analysis. The system was tested in the mapping of properdin deficiency, an X-linked condition with increased risk for a severe infection in the affected.

DNA, Satellite↗
PubMed1975

Activation of the alternative (properdin) pathway by divalent cations.

Mg++, Mn++ and Co++ activate the C system as judged by the reduction in cobra venom factor indeed hemolysis, and cleavage of properdin factor B and C3. The maximum effect requires the addition of 5 to 10 mM of these cations to dialyzed sera respond in similar fashion indicating that these divalent cations can trigger the alternative pathway without the addition other activating agents.

Animals↗
PubMed1976

A properdin system intermediate formed by zymosan and serum at 0 degrees C.

The interaction of guinea pig or rat serum with Z at 0 degrees C leads to the formation of properdin pathway intermediate, ZPI, whose activity is assessed by its capacity to deplete the titer of cobra venom inducible lysis in diluted rat serum. The formation of ZPI does not require C1 or C2 and is not diminished by prior absorption of the serum with Z. In contrast, removal of P suppresses ZPI formation. Both Ca++ and Mg++ are essential cofactors for the formation of this intermediate whose function is abrogated in the presence of anti-C3, anti-P, but not by anti-Factor B. Since C4-deficient guinea pig serum is also effective in ZPI formation, the data suggest that ZPI is an alternative pathway intermediate containing both P and C3.

Animals↗
PubMed1982

Properdin factor B and acute lymphocytic leukemia (ALL).

One hundred-sixty-four ALL patients were compared to 545 controls for differences in phenotype and gene frequencies at the Properdin factor B locus. In addition, 90 of the ALL patients were immune phenotyped. A significant association with the Bf F allele and ALL was found, resulting in an estimated relative risk of 3.62. There was no difference in the Bf S phenotype between ALL patients and controls. However, those homozygous for the Bf S allele are at a significantly low risk of 0.30 for developing ALL. ALL patients with a non-B/T cell type were 2.5 times more likely to be Bf SS homozygotes; in contrast, those patients with the pre-B cell type were 2.5 more likely to be Bf FF homozygotes. These data suggest association of the Bf locus with an ALL protection and/or susceptibility gene(s).

Alleles↗
PubMed1979

Population genetic data on properdin factor B (Bf) in northern Germany.

Properdin factor B phenotypes were determined in 1,112 unrelated individuals and in 151 mother/child combinations from Northern Germany. Gene frequencies were : F = 0.1960, S= 0.7905, F1 = 0.0072, S1 = 0.0063. The data of the mother/child combinations are in full accordance with the postulated gene model.

Adult↗
PubMed1978

Properdin factor b-polymorphism in the population of Hessen, Germany.

The polymorphism of properdin factor B (Bf, C3 proactivator) in a population sample from Hessen, Germany has been investigated by agarose gel electrophoresis and immunofixation. In 522 unrelated individuals seven different phenotypes were observed and the following allele frequencies calculated: BfS = 0.7998, BfF = 0.1772, BfS0.7 = 0.0163 and BfF1 = 0.0077. Investigations of 100 families with 198 children and 30 mother-child combinations support the assumed autosomal codominant way of inheritance.

Adult↗
PubMed1982

Polymorphism of properdin factor B in Japanese. Description of a rare variant and data of association with HLA and C2.

Polymorphism of the properdin factor B (BF) was investigated using an agarose gel immunofixation electrophoresis in 487 unrelated healthy adult Japanese who were already typed for HLA-A, -B, -C and C2. Besides the previously reported phenotypes in Japanese (S, FS, and F), a rare heterozygous phenotype (tentatively maned FTS) was observed once. The estimated allele frequencies for BS*S, BF*F, and FB*FT (F Tokyo) were 0.801, 0.198, and 0,001 respectively. The relative electrophoretic mobility of the variant band of type FTS was measured by Dr. G Mauff to be F 0.75. The conversion fragment Bb of the type showed a double-banded pattern. BF hemolytic activity of the FTS individual was at the same level as other phenotypes. Statistical tests for the phenotypic data of BF with HLA-A, -B, -C, and C2 indicated the presence of the following significant associations in Japanese: Aw33-BF*F, A11-BF*S, Aw24-BF*S, B15-BF*F, B17-BF*F, Bw44-BF*F, B7-BF*S, Bw52;-BF*S, BW54-BF*S, BW59-BF*S, Cw3-BF*F, C2*AT-BF*F, and C2*A'-BF*F.

Adult↗