Fc epsilon RII and IgE-dependent activation of inflammatory cells.
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Animals↗
Biomedical subjects
A Capron
Publications and source records attributed to A Capron.
Characterization of major surface and excretory-secretory immunogens of Trypanosoma cruzi trypomastigotes and identification of potential protective antigen.
The surface antigens of Trypanosoma cruzi trypomastigotes were identified by immunoprecipitation and were compared with metabolically labelled excretory-secretory products (ES) released by the parasites in vitro. A series of major immunogenic components in the ES antigens were revealed (160 kDa, 130 kDa and 80-110 kDa). The trypomastigote surface also bears the 130 kDa band and the 80-110 kDa complex. Competition experiments demonstrated the common antigenic structure of the ES and the surface antigens. Two-dimensional analysis of ES antigens immunoprecipitated by human Chagasic serum revealed several spots in the 80-110 kDa region with a wide range of isoelectric points (PI between 5.4 and 6.7). This reflects a charge heterogeneity of these polypeptides. The trypomastigote 85 kDa polypeptide was also identified in the ES antigens by using a monoclonal antibody against this antigen. Two-dimensional analysis of the 85 kDa proteins shed from the surface of trypomastigotes and immunoprecipitated by the monoclonal antibody 155D3 showed 2 major spots: a major part of the 85 kDa polypeptide was found at pH 6.5-6.6, whereas a substantial amount of the antigen was found at pH 5.7. An additional component with molecular weight of approximately 58 kDa and isoelectric points of 6.5 and 6.6, was also visualized. Detection of the 85 kDa polypeptide circulating in serum from patients with acute and chronic Chagas' disease was achieved using an enzyme-linked immunosorbent assay. In addition, the data obtained showed that a polyclonal antibody to the 85 kDa polypeptide could be used to passively induce a partial protection of Fischer rats against acute lethal infection. Thus, the antigens recognized by polyclonal antibody appear to play a role in the development of protective immunity against T. cruzi.
Animals↗
The abnormal in vitro response to aspirin of platelets from aspirin-sensitive asthmatics is inhibited after inhalation of nedocromil sodium but not of sodium cromoglycate.
1. Blood platelets from patients with aspirin-sensitive asthma (ASA) generated cytotoxic mediators in the presence of aspirin. This abnormal in vitro response to aspirin was abolished within 1 h after nedocromil sodium inhalation but not after sodium cromoglycate inhalation. 2. Platelets recovered this reactivity to aspirin by 12 hours after nedocromil sodium treatment of ASA-patients. 3. The in vitro reactivity to aspirin of ASA platelets isolated before inhalation was inhibited in the presence of serum isolated 15 and 60 min after nedocromil sodium inhalation.
Administration, Inhalation↗
High levels of soluble interleukin-2 receptor in the serum of 30 patients with idiopathic hypereosinophilic syndrome.
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Eosinophilia↗
Short-term decrease of skin-test sensitivity after rush desensitization in Hymenoptera venom hypersensitivity.
Thirty-seven patients with a history of systemic anaphylactic stings were desensitized by the rush method. Patients were evaluated by skin testing twice, before and 6 weeks after desensitization. An additional control group of 10 patients, not yet desensitized, were tested for skin test technique reproducibility at 6-week intervals. Results were compared with IgE and IgG antibody levels, and with platelet reactivity towards specific Hymenoptera venom. Before desensitization, the maximum skin-test sensitivity was observed at 10(-5) micrograms venom/ml in 56% of patients and decreased to 10(-1) micrograms venom/ml after desensitization (48.6% of patients). Decrease of cutaneous tests was observed in 28/37 patients (75%) (P less than 0.001) and was not associated with significant variations of specific IgE or IgG antibody levels, but was correlated with the decrease of platelet reactivity (P less than 0.05). Conversely, variations of skin-test sensitivity in the control group was not significant.
Adolescent↗
Plasmapheresis in a patient with severe asthma associated with auto-antibodies to platelets.
Although the pathogenesis of aspirin-sensitive asthma remains to be specified, it is known that in the presence of acetylsalicylic acid or non-steroidal anti-inflammatory drugs, platelets from aspirin-sensitive asthmatics have been described as generating cytocidal mediators that killed parasite targets such as Schistosoma mansoni larvae. Here we report, in a patient with corticosteroid-dependent asthma associated with aspirin sensitivity, the presence of circulating IgE antibodies against 55 kD and 68 kD platelet antigens. In addition, the serum from this patient was shown to contain a factor able to trigger the release of cytocidal mediators from his platelets as well as from normal individual platelets. This platelet stimulatory activity was presumably supported by IgE antibodies or immune complexes. After informed consent the patient was submitted to plasma exchanges. Plasma removal induced clinical improvement, anti-platelet antibody decrease, and the reduction of the platelet stimulatory activity. All clinical symptoms disappeared within 2 weeks. The disease remained quiescent for 2 months, and daily requirements for prednisone (20-5 mg), and beta-agonist (10-16 to 0-1 inhalations) could be kept at a low level follow-up. The plasma exchanges were delayed by 3 mg kg-1 azathioprine with the maintenance of clinical improvement. A relapse occurred after the arrest of immunosuppressive therapy with the reappearance of both asthma attacks and anti-platelet antibodies, as well as the increase of the platelet stimulatory activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
The neuropeptide substance P stimulates the effector functions of platelets.
Sensory neuropeptides, such as substance P, appear as potent mediators of various immunological reactions, and inhibit or stimulate a wide range of functions of immune inflammatory cells. Platelets were recently shown to participate as effector cells in an IgE or lymphokine-dependent killing of parasites. Substance P and its carboxy-terminal fragment SP (4-11) induce the cytotoxic activity of platelets towards the larvae of Schistosoma mansoni, respectively, by 90% and 40%, whereas the modified C terminal SP, the SP-free acid, exhibits no effect on the platelets. The neuropeptide effects occur at low doses (10(-8) M), are specific as shown by inhibition studies with a substance P antagonist, the D-SP. Binding data obtained after flow cytofluorometry with FITC-SP lead to the conclusion that SP binds specifically to about 20% of the homogenous population of platelets. Moreover, IgE could modulate the SP-dependent functions of platelets since the pre-incubation with myeloma human IgE or with AP2 monoclonal antibodies--known to inhibit the IgE-dependent killing of these cells-leads to a dramatic decrease of the SP dependent cytotoxic activity of platelets towards the larvae. These findings identify a potent mechanism for nervous system regulation of host defence responses.
Amino Acid Sequence↗
Presence of antibodies against endothelial cells in the sera of patients with episodic angioedema and hypereosinophilia.
We reported three additional cases of a newly described syndrome called episodic angioedema with hypereosinophilia. In order to investigate its pathophysiological mechanisms, four parameters were concurrently investigated, including blood eosinophil density, serum chemoattractant activity, serum major basic protein (MBP) levels and the presence of anti-endothelial cell antibodies. Distribution of eosinophils through a metrizamide density gradient showed a preferential sedimentation of blood eosinophils in intermediate layers, clearly different from the hypodense cells (low-density layers) identified in a group of seven patients with idiopathic hypereosinophilic syndrome (HES). In two of the three patients with cyclic angioedema, a chemotactic activity towards eosinophils was detected in the serum (30 +/- 6 and 42 +/- 12 eosinophils per high-power field; P less than 0.05 compared with a control group). Serum MBP levels were at 1524, 619 and 1200 pg/ml. All three patients had circulating anti-endothelial cell antibodies, predominantly of the IgG isotype, in contrast to controls (P less than 0.01) or to patients with HES (P less than 0.01). Specificity of the antibody for endothelial cells was demonstrated in the three patients studied by the absence of binding to various blood cells, including monocytes, lymphocytes, eosinophils and platelets. In one case (patient 2), the levels of anti-endothelial cell antibodies, as well as the serum chemoattractant activity to eosinophils varied according to the successive acute phases of the disease. Although further investigations are needed to clarify the exact pathophysiology of this syndrome, and especially the possible participation of the anti-endothelial cell antibodies in the cutaneous lesions, these data suggest that angioedema observed in this syndrome could result from the combined effects of activated eosinophils and of immunologically induced endothelial lesions.
Adult↗
A synthetic protein corresponding to the entire vpr gene product from the human immunodeficiency virus HIV-1 is recognized by antibodies from HIV-infected patients.
The 95 amino acid-protein encoded by the non-structural vpr gene of the human immunodeficiency virus type 1 (LAV-1BRU isolate) was chemically synthesized by solid phase methodology. The synthetic vpr protein was characterized by amino acid analysis, sequence analysis, RP-HPLC, and urea-SDS PAGE. Using a radioimmunoassay, antibodies to the synthetic protein were detected in sera of 25% of HIV 1-seropositive patients tested. Western blot analysis suggested that the antibodies preferentially recognize the dimeric form of vpr.
Amino Acid Sequence↗
Protection of nude rats against Toxoplasma infection by excreted-secreted antigen-specific helper T cells.
In the present work we demonstrate the implication of excreted-secreted antigens in eliciting the protective cell-mediated immunity developed by rats toward Toxoplasma gondii. We first showed that 10(4) specific T cells from T. gondii-infected rats conferred to nude rats the ability to resist an infection by the highly virulent RH strain of T. gondii. In a second series of experiments, the role of excreted-secreted antigens in this protection was demonstrated. After the adoptive transfer to nude rats of various doses (10(3), 10(4), 10(5)) of excreted-secreted antigen-specific helper T cells (propagated in vitro during one month), significant protection toward T. gondii was induced. Moreover, these cells were responsible for a specific antibody response in nude rats, which are normally unable to develop any specific humoral response. The specificity of these antibodies was directed toward different molecules with molecular masses of 104, 97, 57, 39, 30, 21, and 18 kilodaltons; some of these have been previously characterized as major excreted-secreted antigens.
Animals↗
Isotypic profiles of antibody responses to Toxoplasma gondii infection in rats and mice: kinetic study and characterization of target antigens of immunoglobulin A antibodies.
The antibody responses to Toxoplasma gondii were investigated in rat and mouse experimental models. The immunoglobulin A (IgA) antibody response was of particular interest because acquisition of Toxoplasma gondii is usually by the oral route. The rat model was used because the natural resistance of rats to the parasite is similar to the natural resistance exhibited by adult humans. There was an early and simultaneous rise in IgA and IgM antibody responses. The IgA antibody response was maximal around day 40. IgA antibodies from Fischer rats were mainly directed against soluble and membrane antigens of 28.5, 29, 30, 35, and 38 kilodaltons (kDa). In mice, however, a major antigen of 29 kDa was recognized by IgA antibodies. Moreover, in orally infected rats, an intense IgE antibody response against the major surface antigen, P30, was observed. An IgA antibody response was also observed in rats and mice immunized with Toxoplasma excreted-secreted antigens, even without adjuvant. This response was mainly directed against 28.5- and 34-kDa antigens in rats. Serum IgA from infected rats tested against the excreted-secreted antigens bound to 28.5- 34-, and 39-kDa antigens, whereas sera from infected mice recognized only the 34-kDa antigen.
Animals↗
Protection of rats against Schistosoma mansoni infection induced by platelets stimulated with the murine recombinant tumor necrosis factor alpha.
Human recombinant tumor necrosis factor (rTNF alpha) and lymphotoxin (rTNF beta) have been shown to enhance the schistosomicidal activity of human platelets in vitro. In this report, we demonstrated that the murine rTNF was able to induce the in vitro cytotoxic activity of both murine and rat platelets towards the larvae of Schistosoma mansoni, whereas human rTNFs activated only the murine platelets. Passive transfer of platelets stimulated with murine rTNF significantly protected rats up to a 65% reduction of the worm burden. Thus, rTNF may constitute, via its interactions with effector cells, an important regulatory mechanism during the parasitic infection of rats.
Animals↗
T-cell responsiveness towards various synthetic peptides of the P28 antigen in rat and mouse models during Schistosoma mansoni infection.
It has recently been demonstrated that the Schistosoma mansoni P28 antigen can induce a strong protective immunity after direct immunization in various experimental models. T lymphocytes from Fischer rats immunized with the recombinant P28 antigen were cultured in vitro in the presence of seven synthetic peptides derived from the amino acid sequence of the P28. The most significant and reproducible proliferation was obtained with the 24-43 and 115-131 synthetic peptides. In order to analyze whether these located determinants were also exposed to the host's immune system during the natural S. mansoni infection or after immunization with crude antigenic extracts of various development stages of the parasite, the T-cell responsiveness of infected or immunized Fischer rats and BALB/c mice was tested towards these synthetic peptides. The results showed that, in both permissive (mouse) and non-permissive (rat) hosts, 24-43 and 115-131 synthetic peptides are recognized during the course of infection and that there is a dynamic variation of this recognition. These peptides are also recognized by T cells educated against crude antigenic extracts of different developmental stages of the parasite which contained the native form of the P28 molecule. Taken together, the results indicated that these synthetic peptides derived from the recombinant P28 antigen can activate T lymphocytes educated against the native P28 molecule during the development and maturation of the parasite in their hosts. Therefore, they might be useful for the construction of synthetic vaccines against schistosomiasis.
Amino Acid Sequence↗
[Presence and functional role of an epitope of the second receptor for IgE (FcE RII) in mast cells and basophils in the rat].
Mast cells and basophils express the high affinity IgE receptor (FcERI) whereas the low affinity receptor for monomeric IgE (FcE RII) is present on macrophages, lymphocytes, eosinophils, platelets and Langerhans cells. Recent studies confirmed that the two receptors were totally distinct. The present work shows that a monoclonal antibody (BB10), able to bind to FcE RII on different cell populations, interacts with FcE RI expressing cells: rat peritoneal mast cells and a rat basophilic leukemia cell line (RBL 2 H 3). The structure recognized by BB10 is distinct from FcE RI and modulates the IgE-dependent histamine release. In conclusion, it appears that a common epitope with FcE RII is present on mast cells and basophils and that a functional relation might exist between this structure and FcE RI.
Animals↗
A monoclonal antibody to Ly-6 gene product inhibits generation of functionally active T cells and recognizes single antigenic specificity whose expression is up-regulated in virus-transformed rat fibroblast.
In order to elucidate the relationship between the structure and function of proteins encoded for by the Ly-6 gene complex, a cDNA was constructed for a Ly-6.2 specificity and then monoclonal antibodies (mAb) generated to bacterially synthesized protein. The addition of one of these mAb, designated Pb-19, inhibited the proliferative response of T cells to concanavalin A (Con A) or major histocompatability complex (MHC) alloantigens. Reactivity of Pb-19 to the Ly-6 specificity was blocked by a known anti-Ly-6.A.2 mAb but not by an anti-Ly-6.E.1 mAb. This mAb detected a Ly-6.A.2 specificity (a 33,000 MW antigen) whose expression was increased in a transformed rat fibroblast containing the entire genome of bovine papillomavirus.
Animals↗
[New molecular approaches to the diagnosis and prevention of toxoplasmosis].
Toxoplasmosis, a world wide distributed parasitic disease, is known to cause severe complications in foetuses or newborns from mothers acutely infected during pregnancy. More recently, an increased interest for Toxoplasma infection has come from the high incidence of Toxoplasma encephalitis in patients suffering from AIDS. For many years, research aiming at the development of a vaccine strategy has been concentrating on the identification and molecular characterization of surface antigens of the proliferative stage of the parasite, the tachyzoite. On the basis of our previous experience in other parasitic diseases we have based our research strategy with a particular emphasis given to excretory-secretory antigens (ES), to common epitopes expressed both on tachyzoites and bradyzoites, and to isotype selection. The development of a novel experimental model based on the use of athymic (nude) rats has, on the other hand, allowed by selective reconstitutions with antibodies or cells a detailed analysis of the effector mechanisms involved in resistance. Passive transfer experiments of antibodies or T cells from animals immunized with ES antigens have shown their remarkable immunogenicity whereas direct immunization with ES has led to a highly significant degree of protection in mice. Four major immunogens of 43 kD, 39 kD, 28.5 kD and 23 kD have been identified in E.S. products and shown by various techniques including colloidal gold labelling using monoclonal antibodies, to be common to the tachyzoite and bradyzoite stages and localized in their dense granules. Molecular cloning of proteins has been undertaken.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
The helminth Schistosoma mansoni expresses a peptide similar to human beta-endorphin and possesses a proopiomelanocortin-related gene.
Opioid peptides, a group of transmitter substances with a high degree of phylogenic conservation, have many different functions, including a role in modulation of cells of the immune system. We have postulated the existence of such peptides in the parasite Schistosoma mansoni in view of their possible role in host-parasite interactions. In this report we show that beta-endorphin, which is a member of the opiate family and is derived from the proopiomelanocortin (POMC) precursor, is present in S. mansoni. Southern blots of cercarial genomic DNA, hybridized with two oligonucleotide probes complementary to highly conserved POMC sequences, showed a POMC-related gene in this trematode. Northern blot analysis of adult worm RNA indicated that this gene was actively transcribed. Significant amounts of beta-endorphin, adrenocorticotropin (ACTH), and alpha-melanocyte stimulating hormone (alpha-MSH) were detected in all developmental stages of the parasite by radioimmunoassays with the use of antisera to human peptides. By means of reverse-phase high-performance liquid chromatography (HPLC), we found that the parasite beta-endorphin-like material and the human opiate have a high degree of homology. These results appear to constitute the first demonstration of a POMC-related gene transcribed in an invertebrate.
Adrenocorticotropic Hormone↗