Factor H inhibits complement activation induced by liposomal and micellar drugs and the therapeutic antibody rituximab in vitro.

Hypersensitivity reactions to particulate drugs can partly be caused by complement activation and represent a major complication during intravenous application of nanomedicines. Several liposomal and micellar drugs and carriers, as well as therapeutic antibodies, were shown to activate complement and induce complement activation-related pseudoallergy (CARPA) in model animals. To explore the possible use of the natural complement inhibitor factor H (FH) against CARPA, we examined the effect of FH on complement activation induced by CARPAgenic drugs. Exogenous FH inhibited complement activation induced by the antifungal liposomal Amphotericin-B (AmBisome), the widely used solvent of anticancer drugs Cremophor EL, and the anticancer monoclonal antibody rituximab in vitro. An engineered form of FH (mini-FH) was more potent inhibitor of Ambisome-, Cremophor EL- and rituximab-induced complement activation than FH. The FH-related protein CFHR1 had no inhibitory effect. Our data suggest that FH or its derivatives may be considered in the pharmacological prevention of CARPA

Cardiopoietic cell therapy for advanced ischemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial

Cardiopoietic cells, produced through cardiogenic conditioning of patients' mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort

(Tables 3-4, pages 112-115) Chemical composition of Fe-Mn micronodules from metalliferous sediments of the East Pacific Rise and the Mid-Atlantic Ridge TAG areas

A geochemical study of Fe-Mn micronodules associated with the metalliferous sediments at two spreading centres has shown that their composition depends on the site of micronodule formation. Close to the hydrothermal mounds they exhibit significant variation in elemental content related to the type of hydrothermal discharge (low- or high-temperature), the nature of primary hydrothermal matter (plume fall-out, oxidised sulfides), and the extent of diagenesis. In this environment three types of micronodules can be distinguished although not observed as pure end-members: (1) diagenetic micronodules; (2) micronodules formed generally from the plume fall-out of oxyhydroxide matter; and (3) micronodules grown on the oxidised sulfide grains supplied to the sediments by slumping or fall-out of nearby buoyant plume. Away from the active spreading centre, the hydrothermal signatures of primary precipitates are gradually masked and hydrogenous/diagenetic processes lead the micronodule formation. Composition of micronodules becomes less variable. Well-pronounced, deep rift valleys confine the hydrothermal plume, which brings the hydrothermal suspension into contact with restricted volumes of seawater and, consequently, weakens the hydrogenous influence on the primary hydrothermal matter. Shallow rift valleys do not confine hydrothermal plumes, which are scattered over hundreds of kilometres by bottom currents. This brings the hydrothermal suspended matter into contact with large volumes of seawater. Extensive scavenging occurs, which masks the hydrothermal signal away from the spreading axis and enhances the hydrogenous one. Thus, the ridge crest morphology, defined by the spreading rate, is supposed to play a certain role, though indirect, in the chemical composition of the primary precipitates and, consequently, in the composition of the micronodules formed

Point analysis and provenance of ceramics: a first approach

International audienc

Cosmic spherules from metalliferous sediments: a long journey to the seafloor

The iron cosmic spherules found in the metalliferous sediments of two spreading centers (Mid-Atlantic Ridge and East Pacific Rise) represent different stages of the four-step model suggested by Bi et al. (1993). The occurrence of one spherule with a conic tail and the detailed study of the whole spherule set allow the development of the “Dong Bi” model. If an interplanetary body (iron or iron-rich stony meteorite) has hypervelocity and enters the Earth’s atmosphere under low incidence angle, the path of its derivates to the Earth’s surface will be long. This will provide possibilities for development of the next, fifth step of the “Dong Bi” model: iron oxide shell reversal and formation of a conic tail. If the flight of the iron oxide spherule continues after the first 4 stages (ablation, oxidation, core protrusion, and core detachment) it reverses with its light hollow part back. The surface layer of the front side of the spherule ablates. The removed liquid droplets, entrained in a trail after the flying spherule, crystallize in the antipodal zone of rarefaction capping the hollow with a conic tail

Contribution of PIGE technique to the study of obsidian glasses

International audienc

The Murine Factor H-Related Protein FHR-B Promotes Complement Activation

Factor H-related (FHR) proteins consist of varying number of complement control protein domains that display various degrees of sequence identity to respective domains of the alternative pathway complement inhibitor factor H (FH). While such FHR proteins are described in several species, only human FHRs were functionally investigated. Their biological role is still poorly understood and in part controversial. Recent studies on some of the human FHRs strongly suggest a role for FHRs in enhancing complement activation via competing with FH for binding to certain ligands and surfaces. The aim of the current study was the functional characterization of a murine FHR, FHR-B. To this end, FHR-B was expressed in recombinant form. Recombinant FHR-B bound to human C3b and was able to compete with human FH for C3b binding. FHR-B supported the assembly of functionally active C3bBb alternative pathway C3 convertase via its interaction with C3b. This activity was confirmed by demonstrating C3 activation in murine serum. In addition, FHR-B bound to murine pentraxin 3 (PTX3), and this interaction resulted in murine C3 fragment deposition due to enhanced complement activation in mouse serum. FHR-B also induced C3 deposition on C-reactive protein, the extracellular matrix (ECM) extract Matrigel, and endothelial cell-derived ECM when exposed to mouse serum. Moreover, mouse C3 deposition was strongly enhanced on necrotic Jurkat T cells and the mouse B cell line A20 by FHR-B. FHR-B also induced lysis of sheep erythrocytes when incubated in mouse serum with FHR-B added in excess. Altogether, these data demonstrate that, similar to human FHR-1 and FHR-5, mouse FHR-B modulates complement activity by promoting complement activation via interaction with C3b and via competition with murine FH