Biomedical subjects

F Maillet

Publications and source records attributed to F Maillet.

62 records · Page 4Linked to original sources

PubMed1983

Heparin prevents formation of the human C3 amplification convertase by inhibiting the binding site for B on C3b.

Fluid-phase heparin prevents generation of the C3 amplification convertase of human complement, C3b, Bb most likely by inhibiting the formation of the bimolecular complex between cell-bound C3b and B. The effect of heparin on the binding of B to C3b was examined using 125I-labelled B and C3b-bearing sheep erythrocytes (EsC3b). In the absence of heparin, B bound to EsC3b with an affinity of 0.5-1 X 10(6) M-1 in the presence of 5 mM Mg2+. Incremental amounts of heparin (100-700 micrograms/10(7) EsC3b) inhibited the binding of 125I-B to C3b in a dose-dependent manner. Scatchard analysis of the binding data in the presence of four inhibitory concns of heparin revealed that heparin did not affect the binding affinity of B for C3b but decreased the number of C3b sites recognized by B on the cells. No inhibition of binding occurred in the presence of totally (N- and O-) desulfated heparin which has no anticomplementary activity. These results demonstrate that heparin prevents generation of the C3 amplification convertase by binding to cell-bound C3b and masking the binding site for B on C3b.

Animals↗

PubMed1983

Modulation of the formation of the human amplification C3 convertase of complement by polycations.

Neutralization of the negative charges of heparin by polycations in the fluid phase suppressed the inhibitory effect of heparin on the generation of the C3b-dependent amplification convertase of complement C3b,Bb. Polymeric polycations alone, whether natural or synthetic, prevented formation of the cell-bound amplification convertase and of the fluid-phase interaction of C3b, B and D, in a dose-related fashion in the concentration range of 1 to 2 X 10(-8)M for poly-L-lysine (PLL) 50,000. The inhibitory effect of PLL on formation of the cell-bound convertase was independent of the presence of P. Percent inhibition of C3b,Bb,P and C3b,B,P formation was constant when the convertases were formed with a fixed concentration of PLL and increasing amounts of B; PLL was more effective in preventing convertase formation on cells bearing low numbers of C3b and developed with high doses of B. The decay of the preformed P stabilized convertase was not altered by PLL whether in the presence or absence of H. Thus, polycations in the fluid phase specifically inhibit formation of the amplification C3 convertase by preventing the association between C3b and B, most likely by acting on C3b. The low-affinity interaction between C3b and B is a privileged site for natural or pharmacological modulation of complement by polyelectrolytes.

Complement Activating Enzymes↗

PubMed1982

Guinea pig erythrocytes, after their contact with influenza virus, acquire the ability to activate the human alternative complement pathway through virus-induced desialation of the cells.

Guinea pig erythrocytes that had been exposed to influenza A virus activated the alternative complement pathway in whole human serum in the absence of natural antibodies. Because all virus particles were eluted from the treated cells, activation was not dependent on antiviral antibodies or on virus particles themselves. The relative capacity of treated erythrocytes to activate the alternative pathway was dependent on the amount of virus to which the cells had been exposed and was directly related to the amount of sialic acid removed from the erythrocyte membrane during incubation with either whole virus particles or purified viral sialidase. C3b bound to cells that had been treated with virus, and P-stabilized amplification convertase sites P,C3b,Bb formed on these cells, exhibited increased resistance to the action of the regulatory proteins beta-1H and C3b Ina compared with C3b and P,C3b,Bb on untreated, nonactivating cells. The acquired resistance of the cell-bound, P-stabilized amplification convertase to decay-dissociation by beta-1H was directly related to the activating capacity of the treated cells in whole serum (r = 0.95) and to the amount of sialic acid removed from the cells by the virus (r = 0.98). Desialation represents a specific alteration of the cell surface by which a nonimmune host, through activation of the alternative pathway, may deposit C3b on a target cell that had been exposed to influenza virus and may lyse virus virus-modified cells during orthomyxovirus infections.

Animals↗

PubMed1981

Modulation of the formation of the human C-3 amplification convertase of complement by polyelectrolytes.

Heparin in the fluid phase inhibits generation of the C3 amplification convertase of complement C3b,Bb. The anticomplementary activity requires the presence of O-sulfate groups on the molecule and is suppressed when the negative charges of heparin are neutralized with positive charges on polycations. In the absence of heparin, polycations inhibit generation of the cell-bound or fluid phase amplification convertase at final concentrations of 1 to 2 x 10(-8) M for poly-L- lysine 50,000 (PLL). PLL is more active on the D-dependent convertase C3b,Bb than in preventing generation of C3b,B; it does not alter the stabilizing effect of properdin. As for heparin, the major site of the inhibitory action of polycations is on the binding capacity of C3b for B. The low affinity interaction of C3b and B is a privileged site for potential pharmacologic modulation of the amplification convertase of complement by polyelectrolytes.

Binding Sites↗

PubMed1981

[Consumption hypocomplementemia: relation between hemolytic and immunochemical assays of C4 in serum (author's transl)].

The aim of the study is to compare two methods for the measurement of the fourth human complement component through its hemolytic activity and immunodiffusion properties in 35 healthy subjects and 35 patients with immunological complement depletion. For the healthy subjects, the results show a highly significant correlation between the two methods (the coefficient of correlation is + 0.80). On the contrary, there is no correlation between the two assays for the patients suffering from consumption hypocomplementemia. The reasons of this discrepancy are discussed.

Adolescent↗

PubMed1981

[Comparison of consumption kinetics of the C4 and C2 components of complement by immune complexes "in vitro" (author's transl)].

We study the consumption kinetic of the fourth and second component of complement by the C1 esterase in different systems with EA or EAC1 and fresh NHS, or functionally purified C4 and C2 preparations. The results show that the two kinetics are similar with a comparable decrease in both C4 and C2 activities till 90 seconds (the mean residual values are from 21 to 34% at this time). The results show moreover that the consumption of the C2 component requires necessarily the presence of the C4 component. The C4 reaction kinetic compared with the C2 "in vitro" one refutes the hypothesis of a greater sensitivity of the C4 component compared with the C2, for the enzymatic action of the C1 esterase. So, a discrepancy in the reaction speed cannot be evoked in order to explain the obvious C4 depression in the consumption hypocomplementemia, and different hypothesis have to be investigated, such as, for instance, a lower synthesis rate of the C4 component compared with the C2 one.

Animals↗

PubMed1979

[Consumption hypocomplementemia: comparative value of haemolytic and protein estimations of the components of the classical pathway (author's transl)].

Titrations of total complement (CH50) and of the different components of the classical pathway of the complement system in patients with supposed consumption hypocomplementemia, show that the complement depression involves in an order of decreasing severity hemolytic C4, hemolytic C2, total complement, hemolytic C1, protein C4 and protein C3. These results as well as correlative studies between these different parameters suggest that C4 is the most specific target of activited C1 esterase (C1s). They stress the interest of hemolytic titrations as well as the strong limitations of protein titrations.

Adolescent↗

PubMedDate not supplied

Sulfonated dextran inhibits complement activation and complement-dependent cytotoxicity in an in vitro model of hyperacute xenograft rejection.

In the present study, we demonstrate that a substituted soluble dextran derivative bearing 73% carboxylic groups and 15% benzylamide sulfonate groups, termed CMDBS25, inhibits complement activation and complement-mediated damage in an in vitro model of xenogeneic rejection. Incubation of porcine aortic endothelial cells with normal human serum resulted in time-dependent complement consumption as assessed by C3a generation in the fluid phase and deposition of activated complement fragments C3, C5 and of C5b-9 on target cells. The presence of C5b-9 membrane attack complex was associated with 51Cr release from prelabelled endothelial cells. The addition of 5-25 mg of CMDBS25/ml under the experimental conditions used, inhibited complement activation and C3a generation in a dose-dependent fashion. CMDBS25 (25 mg/ml) totally suppressed iC3b, C5 and C5b-9 cytolytic complex deposition on cells and inhibits by 42% lysis of target endothelial cells. Native dextran had no effect. Our observations document the anti-complementary properties of sulfonated dextran derivatives and their potential as therapeutic agents for the prevention of complement-dependent hyperacute xenograft rejection.

Animals↗