María M. E. de Bracco

Argentine hemorrhagic fever. Alterations of the complement system and anti-Junin-virus humoral response.

Abstract We investigated immunologic mechanisms and the role of complement in the pathogenesis of Argentine hemorrhagic fever, a disease caused by the Junin virus, a member of the arenavirus group. Total serum complement activity was reduced to 68 per cent of control values in patients with severe or moderate disease (P<0.001). C2, C3 and C5 values were also low (12 to 60 per cent) during the early acute period of the disease. However, serum C4 content was increased to 160 per cent of the control values in the same patients. Total complement activity returned to normal with clinical and laboratory recovery, at the time of detection of antibodies against Junin virus. C1q reactive material was found in four of 19 cases and no relation to the evolution of the disease could be established. These results suggest that immune complexes are not important in the pathogenesis of Argentine hemorrhagic fever, but that activation of the complement system has a role. (N Engl J Med 299:216–221, 1978)

Effect of phytohemagglutinin-stimulated human lymphocytes on isolated rat atria

SummaryThe effect of phytohemagglutinin (PHA) stimulated human lymphocytes on the contractile activity of isolated rat atria was studied. Increased isometric developed tension (IDT) and higher frequency of contractions (FC) were observed shortly after contact of PHA-activated lymphocytes with spontaneously beating rat atria. Since pre-exposure of the lymphocytes to PHA was not necessary and the pharmacologic effects were demonstrated immediately after addition of the lectin, division of the effector cells as a requisite for their action was excluded.Experiments performed with the antibiotic crystallized fromStreptomyces chartreusenis, Ca2+-ionophore A-23187, yielded similar effects.Lymphocyte fractionation studies showed that T-lymphocyte-rich and T-lymphocyte-depleted cell fractions had opposite effects on IDT and FC. The inotropic and chronotropic effects were not modified by (−)-propranolol or antihistaminics. Inhibitor of the synthesis of prostaglandins enhanced the action of PHA-activated lymphocytes but inhibitors of the lipoxygenase pathway: 5,8,11,14-eicosatetraynoic acid (ETYA) and nordihydroguaiaretic acid (NDGA) prevented the increment of IDT and FC. Also, FPL55712, an antagonist of SRS-A abolished the positive inotropic and chronotropic effects of PHA-activated lymphocytes on rat atria. Therefore, a central role for SRS-A in this reaction is suggested.

Mechanisms of activation of complement by extracts of Aspergillus fumigatus.

The extent of complement depletion by Aspergillus fumigatus extracts (AFE) was smaller in hypogammaglobulinemic than in normal human sera, suggesting that γ-globulins play a role in this phenomenon. The titers of Cl, C4 and C2 were reduced after reaction with AFE indicating that complement activation followed the classic pathway. The alternate pathway was also involved since AFE caused conversion of both C3 and factor B in the sera of Clr- and C2-deficient patients and in normal human serum in the presence of EGTA. Similar conversions were observed with hypogammaglobulinemic sera. Heating the AFE at 100°C for 30 min abolished their ability to activate the classic but not the alternate pathway. Hydrazine-sensitive factors were required by AFE to activate the C3 bypass.

Reaction of human lymphocytes with aggregated IgG columns: Effect on antibody-dependent cytotoxicity and EAC rosette formation☆

Abstract Purified human lymphocytes were incubated with Degalan beads coated with aggregated gammaglobulin (DHGG) or DHGG reacted with human complement (C) (DHGG-C). Antibody-dependent cell cytotoxicity (ADCC) and the proportion of C receptor lymphocytes (CRL) in the eluted cells were assayed and compared to cells before treatment or after filtration through control uncoated Degalan bead columns. Antibody-dependent cell cytotoxicity was decreased in cells eluted from DHGG columns and unchanged in cells eluted from DHGG-C columns. On the other hand, the proportion of CRL was reduced to 50% of the original value in DHGG-C eluted cells and it was similar to that of controls in cells eluted from DHGG columns. Inhibition of CRL by DHGG-C did not occur when the incubation was performed at 4 °C or when the DHGG-C beads had been pretreated with anti-C3 antiserum. In contrast, ADCC was reduced when the reaction with DHGG beads was performed either at 37 or 4 °C or when DHGG and DHGG-C beads had been pretreated with anti-HGG and anti-C3 antisera. The data presented in this paper provide evidence for the independence of some functions of the Fc and C3 receptors of human lymphocytes.

Hereditary complement (C2) deficiency with discoid lupus erythematosus and idiopathic atrophoderma.

ABSTRACT. A Family with hereditary deficiency of the second component of complement was studied. Three siblings were homozygous for C2 deficiency and two of them had associated skin diseases. Ono sister presented with idiopathic atrophoderma and the other had clinical and pathological manifestations of discoid lupus erythematosus. This is the first description of an association between idiopathic atrophoderma and C2 deficient state.

Antibody‐dependent cell‐mediated cytotoxicity in rheumatoid arthritis. Effect of rheumatoid serum fractions on normal lymphocytes

Reduced antibody-dependent cell-mediated cytotoxicity (ADCC) was demonstrated in lymphocytes of patients with rheumatoid arthritis (RA). Rheumatoid factor (RF) positive sera inhibited ADCC of normal lymphocytes by reacting both with effector and target cells (sensitized chicken red blood cells). These sera were fractionated by specific adsorption or gradient ultracentrifugation, and isolated RF or RF negative fractions were tested for their ability to inhibit ADCC by reacting with normal human lymphocytes or target cells. RF was ineffective on normal lymphocytes but it strongly inhibited the reaction by interaction with target cells. IgG RF negative fractions of certain sera were inhibitory by direct interaction with effector cells.

Trypanosoma cruzi: Nifurtimox's effect on infectivity

Abstract Mice were protected from infection with Trypanosoma cruzi , Tulahuen strain, by Nifurtimox [3-methyl-4-(5′-nitrofurfurylidene-amino)tetrahydro-4 H -1, 4-thiazine-1,1-dioxide] treatment with doses currently used for human therapy (10 mg/kg/day). The effectiveness of Nifurtimox was reflected by a significant decrease in the mortality of treated infected mice. However, inocula of T. cruzi pretreated in vitro for 7 to 48 hr with the drug at concentrations comparable to those reached in vivo in the peripheral blood of protected mice were as infective as controls, in spite of alterations in the growth of the parasites. In vitro incubation of the parasites up to 48 hr with plasma obtained from Nifurtimox-treated uninfected mice did not reduce their infectivity. These results suggest that the protective effect of Nifurtimox on experimental infection by T. cruzi is not exerted solely by direct trypanocidal action. Whether the action depends on the long-lasting effect of the drug on parasite growth, on the modification of the host, or both remains to be established.