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L Halbwachs-Mecarelli

Publications and source records attributed to L Halbwachs-Mecarelli.

48 records · Page 3Linked to original sources
PubMed1988

C3b receptor (CR1) on phagocytic cells from SLE patients: analysis of the defect and familial study.

In vitro CR1-dependent phagocytosis of C3b-coated erythrocytes, by monocytes and PMN, was found to be significantly decreased in SLE patients. This was in many cases related to a specific defect of CR1 receptors, since the FcR-ingestion of EIgG was normal. On the other hand, CR1 levels of PMN stimulated by FMLP were also found to be decreased in SLE patients, while both the expression of circulating PMN (cells isolated at 4 degrees C) and the total cellular CR1 content were normal. On the basis of the available data, we propose that the impaired phagocytosis is due to a functional defect of CR1 or a defective anchorage of the receptor to the plasma membrane, possibly related to the decreased capacity of CR1 to be up-regulated by FMLP. To study the importance of the genetic background in the CR1 abnormalities, the families of 22 young SLE patients, in which the onset of the disease had occurred before the age of 15, were studied. The expression of CR1 on erythrocytes, and the total CR1 content of PMN, in parents and siblings of these patients did not differ significantly from normal controls. By contrast, the ingestion of EIgGC3b by PMN from healthy relatives of these patients was decreased (65% of the normal mean of PI), while EIgG phagocytosis was normal. A relation between this CR1 functional defect and the familial occurrence of autoimmune disorders is therefore possible.

Erythrocytes↗
PubMed1987

Modulation of neutrophil expression of C3b receptors (CR1) by soluble monomeric human C3b.

Upon incubation at 37 degrees C with purified human C3b (500 micrograms/ml), polymorphonuclear neutrophils (PMN) were found to express up to 50% more C3b receptors (CR1) than PMN incubated with buffer alone. This up-regulation of CR1, assessed by the binding of radiolabeled CR1-specific monoclonal antibody, was dependent on the dose of C3b, occurred within 10-20 min and was stable for at least 90 min. PMN incubated with C3b also demonstrated enhanced CR1-dependent binding functions, such as EC3b rosette formation and phagocytosis of EIgGC3b particles. C3b at a concentration of 500 micrograms/ml induced up to 90% increase in the attachment or the phagocytic index. However, CR1 remained unable to promote phagocytosis of EC3b intermediates. Fc receptor-mediated functions were unaffected by the treatment with C3b. The active factor was characterized as monomeric C3b and, in particular, shown to be distinct from C5a. C3b purified by anion-exchange fast protein liquid chromatography on a Mono Q column or eluted from a monoclonal anti-C3b-Sepharose retained its modulating activity, while native C3 or C3 fragments such as iC3b, C3c or C3d,g were ineffective.

Antibodies, Monoclonal↗
PubMed1986

H deficiency in two brothers with atypical dense intramembranous deposit disease.

We report an H deficiency in two Algerian brothers who had early-onset glomerulonephritis. In addition, one suffered from serious lung infections. The H deficiency was defined by undetectable CH50 and AP50, and low levels of H, C3 and B (less than 10% of normal levels). I and classical pathway components, including C4-bp were normal. CR1 was present on both patients' erythrocytes. No nephritic factor or other circulating alternative pathway activator was detected. The parents, who are first cousins, and a healthy brother and sister had half-normal levels of H. These findings favor an autosomal recessive transmission of the H defect. Although by electron microscopy renal biopsies from both patients were typical for dense intramembranous deposit disease, immunofluorescence microscopy showed an atypical pattern with abundant granular C3 deposits within the mesangium and along the capillary walls. Alternative pathway activators, possibly related to dense deposits, may allow the formation of membrane-associated C3/C5 convertases, unusually stable in the absence of H, since C5, C6, C7, C8 and C9 levels were decreased in both patients. This observation may represent an interesting clue to the relationship between nephritic factor, alternative pathway activation, and dense intramembranous deposit disease.

Adolescent↗
PubMed1986

Defective complement receptors (CR1 and CR3) on erythrocytes and leukocytes of factor I (C3b-inactivator) deficient patients.

In view of a possible modulation of the C3b receptor (CR1) by its ligand, we studied a situation in vivo in which C3b is constantly present in the serum, i.e. the genetic factor I-deficiency. C3b and iC3b receptors (CR1, CR3) on peripheral blood cells, were analysed in three I-deficient (I-def.) patients, from two unrelated families. CR1 and CR3 were quantified by means of monoclonal antibodies, and functionally tested (phagocytosis of sensitized sheep erythrocytes (EIgG) or rabbit erythrocytes (Er), coated with C3b, and chemiluminescence (CL) induced by serum-opsonized zymosan). Erythrocyte CR1 levels were significantly lower in I-def. patients than in normal individuals. Monocytes and polymorphonuclear neutrophils (PMN) prepared at 4 degrees C, to prevent increase of CR1 expression in vitro, expressed low CR1 numbers. Monocytes prepared at room temperature showed a defective CR1-dependent phagocytosis and an impaired CL response, although their CR1 levels were found normal in these conditions. This discrepancy was also observed on phorbol myristate acetate (PMA)-activated cells. These CR1 abnormalities are likely to result from repeated interactions of CR1 with C3b molecules, which circulated in the serum of I-def. patients and were deposited onto their red cells. Although iC3b, the CR3 ligand, is not produced in I-deficient sera, monocyte CR3-dependent function (phagocytosis of unopsonized Er) was also found to be defective in two out of the three patients.

Child↗
PubMed1986

[Subacute septicemia caused by Meningococcus of serogroup Y and acquired deficiency of complement C3 fraction].

The high frequency of meningococcal infections in patients with congenital deficiency of a component of the complement terminal pathway emphasizes the critical role of this system in host resistance against Neisseriaceae. We report the observation of a subacute septicaemia due to N. meningitidis serogroup Y. This girl had an acquired deficit of the C3 fraction of complement due to a high titre of C3 nephritic factor (C3NeF). There was no evidence of partial lipodystrophy or biological symptoms of glomerular disease. The meningococcal infection revealed this biological abnormality.

Child↗
PubMed1986

IgA-affinity purification and characterization of the lectin jacalin.

We describe the use of IgA-Sepharose 4B affinity chromatography to purify the lectin jacalin from saline extracts of Artocarpus integrifolia L. seeds. Elution with 0.8 M D-galactose provides 10-15 mg lectin/50 mg seed protein. Jacalin behaved like a single component on immunoelectrophoresis and a single, somewhat diffuse band was obtained by polyacrylamide gel electrophoresis (PAGE) at pH 4.5. A single peak corresponding to an apparent molecular weight of 43 kDa was obtained by gel filtration on Sephadex G-75 (10 mM phosphate buffered saline (PBS), pH 7.4). On SDS-PAGE +/- 2-mercaptoethanol two bands of apparent molecular weights 11.8 and 14.7 kDa were detected. Jacalin behaved like a protein of apparent molecular weight of 13-14 kDa on Sephadex G-50 eluted with PBS containing 0.2% SDS. These data indicate that the jacalin molecule consists of 3-4 non-identical polypeptide subunits not connected by disulfide bridges. The amino acid composition of IgA affinity-purified jacalin (mol/405 mol amino acids) is Lys (24), His (5), Arg (4), Trp (6), Asx (36), Thr (35), Ser (48), Glx (31), Pro (18), Gly (53), Ala (13), Val (25), Met (3), Ile (23), Leu (25), Tyr (30), Phe (26), which corresponds to a molecular weight of 44.163 kDa.

Amino Acids↗
PubMed1985

Charge and size of mesangial IgA in IgA nephropathy.

To characterize the physicochemical properties of the mesangial IgA in primary IgA nephropathy, acid-eluates from percutaneous renal biopsies of 20 patients were examined. The acid-eluates were obtained from 1287 +/- 498 glomerular sections. The IgA content (mean 15 +/- 10 ng) represented 0.4% of the total eluted proteins. To analyze the molecular weight and the charge of eluted IgA, 11 eluates were subjected to high pressure liquid chromatography (at pH 6.8 and/or pH 3.5) and five eluates to isoelectric focusing on agarose. IgA was detected in the fractions by an IgA-RIA. Comparison of the elution profiles at different pH showed a statistically significant decrease of the excluded IgA peak (greater than or equal to 1,000,000 daltons), and a significant increase of polymeric IgA peaks (1,000,000-320,000 and 320,000 daltons) in acidic chromatography, as compared to non-dissociating conditions. Under acidic conditions, polymeric IgA represent 64% of total eluted IgA. Secretory component binding to polymeric IgA was demonstrated in four out of eight eluates tested. The isoelectric point (pI) of eluted IgA ranged from 4.5 to 5.6, contrasting with the broader and more neutral pI of normal serum IgA (4.5 to 6.8). This study shows that the multimeric nature of IgA, the formation of IgA complexes, and the anionic charge of IgA are likely to be involved in the mesangial IgA deposition in idiopathic IgA nephropathy.

Adolescent↗
PubMed1985

Regulation and deregulation of the fluid-phase classical pathway C3 convertase.

Three mechanisms that regulate the formation and function of the fluid-phase classical pathway C3 convertase (C4b2a) have been elucidated: a) a temperature-mediated intrinsic decay of the enzyme; b) an extrinsic accelerated decay mediated by the effect of the serum protein C4b-binding protein (C4-bp); and c) the inactivation of C4b in the C4b-C4b-p complex by the proteolytic action of C3b/C4b inactivator (I), which cleaves the alpha 1-chain of C4b yielding C4d (alpha 2-chain), and C4c (alpha 3-, alpha 4-, beta-, gamma-chains). A fourth mechanism is described based on the observation that the IgG fraction of the serum of certain patients with glomerulonephritis contains a protein that prevents the intrinsic and C4-bp-mediated decay of surface-bound C4b2a. This protein prolongs the half-life of fluid-phase C4b2a from 10 min to more than 5 hr, increasing the utilization of C3. It also inhibits the decay mediated by C4-bp by preventing the dissociation of C2a from the C4b, 2a complex. In addition, I alone or in the presence of C4-bp fails to cleave the alpha 1-chain of C4b in the stabilized C4b, 2a complex. This protective property of the stabilizing factor (NFc) requires the presence of C2a because C4b was not protected unless it was bound to C2a. Therefore, NFc provides a mechanism by which the serum regulatory proteins are bypassed.

Carrier Proteins↗
PubMed1985

Thymic reticulum in mice. IV. The rosette formation between phagocytic cells of the thymic reticulum and cortical type thymocytes is mediated by complement receptor type three.

A phagocytic cell of the thymic reticulum (P-TR) with dendritic shape recently has been isolated and characterized. We have previously shown that P-TR have an important role to play in the constitution of the thymic microenvironment. Indeed, P-TR are able to produce interleukin 1 and prostaglandin E2, both of which regulate thymocyte activation and proliferation. They are able also to stimulate the proliferation of syngeneic thymocytes enriched in the medullary type. In the present paper, we analyze a close relationship which exists between P-TR and thymocytes of the cortical type. About 25% of P-TR are able to bind to thymocytes and to form rosettes. Rosetting thymocytes represent about 5% of the total population and are PNA+, Lyt 1+2+, H-2-, and sensitive to in vivo steroid treatment. Pretreatment of P-TR with anti-Mac-1, a monoclonal rat IgG antibody against mouse macrophages and specific for complement receptor type three (CR3), abolished rosette formation. Rosette formation also was found to be inhibited by zymosan-treated serum containing the CR3 ligand, C3bi, and by certain sugars, in particular, N-acetyl-D-galactosamine and L-xylose. Our results suggest that rosetting thymocytes bind to CR3 on the P-TR membrane and that sugar constituents of the carbohydrate moieties on the thymocyte surface may serve as a recognition site during the binding process.

Animals↗
PubMed1982

Inhibition of alternative pathway factor D by factor B-related synthetic hexapeptides.

Hexapeptides mimicking the partial amino acid sequence of factor B surrounding the bond that is cleaved by factor D have been synthesized. These peptides have been assessed for their ability to inhibit factor D enzymatic activity and for their susceptibility to serine proteases. The synthetic peptides were cleaved by bovine trypsin and C1s but not by alpha-thrombin and factor D. The peptides inhibited factor B cleavage and fluid-phase or cell-bound alternative pathway C3 convertase activation by factor D. Altogether, these results suggest that peptides analogous to factor B specifically inhibit factor D enzymatic activity. Thus, they constitute an interesting tool for study of alternative pathway activation and can be of use when attempting to manipulate this pathway, since factor D is an essential component for alternative pathway initiation and amplification.

Animals↗