Structural Changes Accompanying Enzymatic Activation of Human Hageman Factor

Revak, Susan D.; Cochrane, Charles G.; Johnston, A.; Hugli, Tony E.

doi:10.1172/jci107799

Cited by 148 publications

(63 citation statements)

References 20 publications

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“…6), implying that RGP-l may also activate HF. Kallikrein also activates HF to form ,6-HFa which converts prekallikrein to kallikrein (43)(44)(45)(46)(47)(48). Accordingly, kallikrein generation by RGP-1 in normal plasma could be augmented by this mechanism, while its production by RGP-I in HF-deficient plasma would lack this additional pathway, thus explaining why VPE is reduced relative to normal plasma.…”

Section: Discussionmentioning

confidence: 99%

Pathogenesis of periodontitis: a major arginine-specific cysteine proteinase from Porphyromonas gingivalis induces vascular permeability enhancement through activation of the kallikrein/kinin pathway.

Imamura¹,

Pike²,

Potempa³

et al. 1994

J. Clin. Invest.

169

128

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To elucidate the mechanism of production of an inflammatory exudate, gingival crevicular fluid (GCF), from periodontal pockets in periodontitis, we examined the vascular permeability enhancement (VPE) activity induced by an arginine-specific cysteine proteinase, Ar-gingipain-1 (RGP-1), produced by a major periopathogenic bacterium, Porphyromonas gingivalis. Intradermal injections into guinea pigs of RGP-1 (> 10' M), or human plasma incubated with RGP-1 (> 10-9 M), induced VPE in a dose-and activitydependent manner but with different time courses for the two routes of production. VPE activity induced by RGP-1 was augmented by kininase inhibitors, inhibited by a kallikrein inhibitor and unaffected by an antihistamine drug.The VPE activity in human plasma incubated with RGP-1 also correlated closely with generation of bradykinin (BK).RGP-1 induced 30-40% less VPE activity in Hageman factor-deficient plasma and no VPE in plasma deficient in either prekallikrein (PK) or high molecular weight kininogen (HMWK). After incubation with RGP-1, plasma deficient in PK or HMWK, reconstituted with each missing protein, caused VPE, as did a mixture of purified PK and HMVVK, but RGP-1 induced no VPE from HMWK. The VPE of extracts of clinically isolated P. gingivalis were reduced to about 10% by anti-RGP-1-IgG, leupeptin, or tosyl-L-lysine chloromethyl ketone, which paralleled effects observed with RGP-1. These results indicate that RGP-1 is the major VPE factor of P. gingivalis, inducing this activity through PK activation and subsequent BK release, resulting in GCF production at sites of periodontitis caused by infection with this organism. (J. Clin. Invest 1994. 94:361-367.)

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Section: Discussionmentioning

confidence: 99%

Pathogenesis of periodontitis: a major arginine-specific cysteine proteinase from Porphyromonas gingivalis induces vascular permeability enhancement through activation of the kallikrein/kinin pathway.

Imamura¹,

Pike²,

Potempa³

et al. 1994

J. Clin. Invest.

169

128

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“…The Factor XII fractions, which eluted after the first protein peak, were pooled and adsorbed to DEAE-Sephadex A-50equili-brated with pH 8.1 buffer containing 0.01 M Na2HPO4, 0.005 M EDTA, and 50 ,g/ml Polybrene. Factor XII was eluted with a straight line gradient to pH 4.6 buffer containing 0.15 M NaH2PO4, 0.25 M NaCi, and 0.001 M EDTA according to the method of Revak, et al (14). The pooled Factor XII fraction, which eluted following the initial protein peak, had a specific activity of 595 (% Factor XII/A280).…”

Section: Methodsmentioning

confidence: 99%

Partial purification and characterization of contact activation cofactor.

Schiffman¹,

Lee²

1975

J. Clin. Invest.

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A B S T R A C T The contact phase of intrinsic clotting involves Factor XI, Factor XII, Fletcher factor, and a fourth activity that we call contact activation cofactor (CAC). All four of these activities are reduced or absent in Dicalite-adsorbed plasma. A modified activated partial thromboplastin time assay for CAC has been defined by using a substrate of Dicalite-adsorbed plasma combined with partially purified sources of Factors XI and XII, and Fletcher factor. The following properties of CAC in plasma have been determined by using the assay: it is stable up to 60 min at 56°C; gradually loses activity at 800C; is stable between pH 6 and 9; is precipitated by ammonium sulfate between 40% and 50% saturation; is slightly adsorbed by Al (OH) s; and is eluted from DEAE-cellulose after the major protein peaks. A purification procedure has been devised that separates CAC from other known clotting factors. Isolated CAC was less stable than CAC in plasma, but in the presence of dilute human serum albumin it retained full activity for 80 min at 560C. On gel filtration CAC had an apparent mol wt of 220,000 daltons. These properties are consistent with those described for Fitzgerald factor, which further supports the conclusion that CAC and Fitzgerald factor represent the same activity. Isolated CAC promoted the generation of activated Factor XI (XIa) in a mixture containing purified Factor XI, Factor XII, and kaolin. The amount of Factor XI. generated was proportional to the amount of added CAC. No time-consuming reaction between Factor XI or Factor XII and CAC could be demonstrated.

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“…The initial step involves activation of Hageman factor (6), which, in turn, initiates both the coagulation and fibrinolytic systems. Plasmin digests activated Hageman factor, yielding a 28,000 molecular weight fragment (prekallikrein activator) which converts prekallikrein to kallikrein (30). Kallikrein, in turn, cleaves bradykinin from kininogen.…”

Section: Speculationmentioning

confidence: 99%

A Study of the Plasma Kinin-generating System in Children with the Minimal Lesion, Idiopathic Nephrotic Syndrome

Kallen

Lee

1975

Pediatr Res

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705the present ones which suggest the existence of a photochemical reaction between D N A and bilirubin are somewhat disquieting, particularly when one considers that mutagens and chemical carcinogens derive their biologic activity from the ability to react with DNA. Our results suggest that phototherapy of neonates is a complex process which may generate a number of potentially dangerous genetic side effects. S U M M A R YThe widespread use of phototherapy in the treatment of neonatal jaundice is causing concern because little information is available on its effects on subcellular structure and function. The present study deals with the effects on the macromolecular structure of D N A illuminated in the presence of bilirubin. The results indicate a bilirubin-induced photodegradation of this biopolymer. ExtractAlthough the precise etiologic incitant of the minimal lesion idiopathic nephrotic syndrome of childhood is not known, it is likely that a host mechanism mediates the permeability alterations of the glomerular capillary wall resulting in massive proteinuria. As a first step in examining the possibility that local kinin release may account for the proteinuria in this disorder, two parameters of the plasma kinin-generating system, plasma prekallikrein and kallikrein inhibitor, were assayed during 27 nephrotic episodes in 21 corticosteroid-responsive children. Plasma kallikrein was assayed by means of its esterase activity on a synthetic arginine ester substrate, N-a-tosyl-L-arginine methyl ester (TAMe), after activation of Hageman factor by kaolin. This activity, after subtraction of spontaneous arginine esterase activity (i.e., TAMe esterase activity measured in plasma not exposed to kaolin) is derived from prekallikrein. Plasma prekallikrein activity in 11 normal children was 99.6 + 2.9 pnol TAMe hydrolyzed/ml plasma/hr (mean + SEM). Kallikrein inhibitor was quantified in arbitrary units. Kallikrein inhibitor activity in 11 normal children was 0.94 + 0.04 units.During the overt nephrotic syndrome, before initiation of intensive daily corticosteroid treatment, mean values were: prekallikrein, 58.5 A 7.24 flmol/ml/hr; and kallikrein inhibitor, 0.35 + 0.06 units. After corticosteroid-induced remission occurred, mean values were: plasma prekallikrein, 118.6 + 3.2 pmol/ml/hr; and kallikrein inhibitor, 0.78 + 0.03 pmol/ml/hr. Both parameters were again assayed in 14 of the 21 children after complete cessation of corticosteroid treatment. Plasma prekallikrein was normal, 99.6 * 4.8 flmol/ml/hr; but kallikrein inhibitor was still somewhat depressed, 0.84 + 0.03 units. A subset of 9 patients had marked depression of plasma prekallikrein to levels less than 20 pmol/ml/hr and essentially undetectable inhibitor acGvity. Serum a-2 macroglobulin was elevated in nephrotic patients: mean value during relapse, 862 + 29 mg/100 ml; during corticosteroid-maintaining remission, 615 * 29 mg/100 ml. After cessation of corticosteroids, mean serum level was 481 + 20 mg/100 ml. The proportional reduction of plasma prekallikrein an...

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Structural Changes Accompanying Enzymatic Activation of Human Hageman Factor

Cited by 148 publications

References 20 publications

Pathogenesis of periodontitis: a major arginine-specific cysteine proteinase from Porphyromonas gingivalis induces vascular permeability enhancement through activation of the kallikrein/kinin pathway.

Pathogenesis of periodontitis: a major arginine-specific cysteine proteinase from Porphyromonas gingivalis induces vascular permeability enhancement through activation of the kallikrein/kinin pathway.

Partial purification and characterization of contact activation cofactor.

A Study of the Plasma Kinin-generating System in Children with the Minimal Lesion, Idiopathic Nephrotic Syndrome

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