Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:The neuropeptide substance P stimulates the effector functions of platelets. 169 68

Eosinophils possess low-affinity Fc immunoglobulin E (IgE) receptors (Fc epsilon R2). We have compared platelet-activating factor (PAF) with lyso-PAF, leukotriene B4 (LTB4) and histamine for their ability to influence the binding of a native myeloma IgE to normal-density human eosinophils, using flow cytometry and a fluorescein-conjugated anti-IgE polyclonal antibody. Preincubation with PAF gave a dose- and time-dependent increase in IgE binding optimal at 10(-7) M (P less than 0.01) and 30 min respectively. A smaller but significant effect was observed with LTB4 and histamine (optimal at 10(-7) M (P less than 0.01) and 10(-5) M (P less than 0.05) respectively). Diluent alone or lyso-PAF had no effect. These results suggest enhanced expression of Fc epsilon R2 by stimulated eosinophils. Further confirmation of enhancement was obtained using two functional assays, i.e., cytotoxicity and mediator (LTC4) generation. IgE-dependent cytotoxicity against schistosomula of Schistosoma mansoni was enhanced by prior incubation of normal eosinophils with PAF (optimal at 10(-7) M), but not lyso-PAF. No LTC4 was detectable following incubation of unstimulated eosinophils with S. mansoni coated with specific IgE. Preincubation of these cells with PAF (10(-7) M) resulted in the generation of 4.4 pmol of LTC4 per 10(6) cells. Our data demonstrate that normal-density eosinophil Fc epsilon R2 expression can be up-regulated in vitro by PAF and LTB4 and that these changes are accompanied by enhanced functional properties.
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PMID:Enhancement of the expression of eosinophil IgE receptor (Fc epsilon R2) and its function by platelet-activating factor. 196 15

This study investigated the effect of platelet-activating factor (PAF), leukotriene B4 (LTB4) histamine and formyl-methionyl-leucyl-phenylalanine (FMLP) on immunoglobulin E (IgE) binding and IgE-dependent cytotoxicity of human normal density eosinophils. The binding of a native myeloma IgE to normal human eosinophils was measured by flow cytometry using a fluorescein-conjugated polyclonal anti-IgE antibody. Preincubation with PAF (optimal at 10(-7)M), but not lyso-PAF or FMLP, gave dose-dependent increases in IgE binding. PAF and LTB4 gave significant increases in IgE binding after 5 min preincubation (P less than 0.05); the effect was further enhanced at 30 min (P less than 0.01). This was further confirmed using the rosette assay where PAF and LTB4, but not lyso-PAF or FMLP, gave dose- and time-dependent increases in IgE eosinophil rosettes. Eosinophil cytotoxicity for schistosomula of Schistosoma mansoni, incubated with immune serum, was also significantly enhanced (P less than 0.01) by PAF in a dose-dependent fashion (optimal at 10(-8) M). Schistosomula coated with FPLC-purified IgE fractions were susceptible to killing by normal density eosinophils, and this was enhanced with PAF (10(-8)M), LTB4 (10(-7)M) and histamine (10(-5)M) but not with FMLP (10(-7)M) or lyso-PAF. IgE-dependent cytotoxicity was confirmed by the removal of contaminating IgG from IgE-rich fractions, and by the abolishment of IgE-dependent cytotoxicity after IgE adsorption. These results suggest that PAF (and to a lesser extent LTB4 and histamine) increase IgE binding, IgE-dependent adherence and cytotoxicity of normal human eosinophils. Although IgE receptors have not been identified, the data support current concepts that certain biological properties of eosinophils may be IgE associated.
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PMID:The effect of platelet-activating factor on IgE binding to, and IgE-dependent biological properties of, human eosinophils. 237 21

We have purified a 28,000 dalton (P28) protein from Schistosoma mansoni adult worms and used it to immunize Fischer rats. Immunofluorescence assays demonstrated that the P28 antigen was mainly located in the parenchyma of the schistosomulum and of the adult worm, including the dorsal spines of the parasite. Western blot analysis revealed that this antigen was present in three species of schistosomes: S. mansoni, S. japonicum, and S. bovis. The antibody response raised against this protein was able to kill S. mansoni schistosomula in in vitro cytotoxicity assays in the presence of rat eosinophils. The inhibition of this cytotoxic activity by an aggregated myeloma IgG2a indicated that one of the major isotypes involved in this in vitro model is IgG2a. The passive transfer of P28 antisera induced a significant level of protection against experimental infection. Moreover, we have immunized Fischer rats and BALB/c mice with the purified 28,000 dalton protein and observed a marked decrease (up to 70%) in the parasite burden in both experimental infection models.
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PMID:A purified 28,000 dalton protein from Schistosoma mansoni adult worms protects rats and mice against experimental schistosomiasis. 310 83

A rat monoclonal antibody of IgE isotype (B48-14) raised against Schistosoma mansoni has been generated by the fusion of mesenteric lymph node cells from LOU/M rats immunized with a preparation of adult schistosome worms and IR973F nonsecreting rat myeloma cells. Investigation of the in vitro effector functions of this IgE antibody showed a high level of cytotoxicity against S. mansoni schistosomula in the presence of eosinophils, macrophages, and platelets. A significant level of protection (40 to 60%) against a challenge infection with S. mansoni cercariae was achieved by passive transfer experiment of B48-14 IgE to naive recipient rats. By immunoprecipitation, B48-14 IgE antibodies were shown to react with an antigen of 26 kDa present in excretion-secretion products of schistosomula, previously described as a potential immunogen eliciting a protective IgE response against schistosomiasis.
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PMID:Functional properties of a rat monoclonal IgE antibody specific for Schistosoma mansoni. 310 90

A number of monoclonal antibodies were obtained by fusion of SP2/0 myeloma cells and spleen lymphocytes from mice infected with Schistosoma mansoni. These antibodies were tested for their ability to inhibit acidic, thiol-dependent proteinases previously isolated from Schistosoma mansoni eggs and adult worms. One of the monoclonal antibodies isolated inhibits egg proteinase activity measured in vitro with the use of a low m.w. synthetic substrate. This antibody, which is an IgG1 isotype, does not appreciably inhibit an acidic, thiol-dependent proteinase obtained from the adult stage of Schistosoma mansoni. Immunocytochemical methods with the monoclonal antibody have been used to localize the egg proteinase within a set of "penetration" glands in the unhatched miracidium.
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PMID:A monoclonal antibody from infected mice to a Schistosoma mansoni egg proteinase. 633 21

Monoclonal antibodies (MA) were prepared by the fusion of spleen cells from C57BL/6J mice infected with Schistosoma mansoni with non-secreting SP2 myeloma cells. Clones of fused cells secreting MA reactive with the egg and cercarial antigens (as determined by the enzyme-linked immunosorbent assay), as well as with schistosomules (as determined by immunofluorescence), were injected into pristane "primed" mice to produce ascitic fluid. Cercariae were treated with MA by incubating them in individual MA or a pool of 3 or 4 MA (0.25 ml each) in form of ascitic fluid diluted in 10 ml of snail water for 60-90 minutes prior to snail exposure. Groups of 7-9 mice were exposed to MA-treated cercariae either via the tail or intraperitoneally (i.p.). Control mice were exposed to non-treated cercariae or those which were treated with nonsense ascitic fluid. Maturing adult worms were recovered by the perfusion technique and counted. The results of two experiments indicate that cercariae treated with a pool of 3 or 4 MA fail to penetrate the skin of mice and thus were not able to develop into adult worms. Treatment of cercariae with 1 MA resulted in a very low worm recovery (4.3% of the exposure dose). The rate of worm recovery from mice injected i.p. with pool-treated cercariae was similar to that recovered from control mice. In contrast to control groups, mice injected with MA-treated cercariae had a higher percentage of immature worms which may indicate a possible form of stunting phenomenon associated with MA-treatment.
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PMID:The effect of monoclonal antibodies on Schistosoma mansoni cercarial penetration of mouse skin. 666 11

Monoclonal antibodies directed against Schistosoma mansoni antigens were produced by the in vitro fusion of B lymphocytes, obtained from mice infected with S. mansoni, and SP2/0 myeloma cells. Antibody reactivity was assessed by ELISA binding, utilizing 4 M KCl extracts of cercariae and adult worms, soluble egg antigen (SEA), and purified antigenic preparations, and by indirect immunofluorescence using living schistosomula. The monoclonal antibodies recognized a wide spectrum of antigenic determinants. The specificity of the monoclonal reactivities ranged from high cross-reactivity to extreme restriction, vis-a-vis the distribution of the recognized determinants within genus, species, stages, and purified antigenic preparations. The specificity of reactivity of monoclonal antibodies for a given determinant was greater than that of immune mouse serum. These studies establish the feasibility of the production of large numbers of monoclonal antibodies and of their use of antigen identification. The monoclonal antibodies are available to interested investigators upon request.
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PMID:Characterization of monoclonal antibodies against Schistosoma mansoni. 668 90

Rat IgG2c monoclonal antibodies have been produced after fusion of spleen cells from LOU/C rats infected with Schistosoma mansoni for 5 wk and IRF983F nonsecreting rat myeloma. The cell supernatant of an IgG2c-producing clone (IPLSm3), as well as ascitic fluids induced by this clone, revealed anti-S. mansoni activity detected by immunofluorescence on schistosomula sections. Antigenic analysis performed with IPLSm3 IgG2c antibody allowed to isolate onto the S. mansoni schistosomula surface a 38,000 dalton antigen previously characterized with the protective IPLSm1 IgG2a monoclonal antibody. Although IPLSm3 IgG2c did not exhibit any killing activity in vitro against schistosomula in the presence of complement, macrophages, or eosinophils, it was shown to strongly inhibit the eosinophil-dependent cytotoxicity mediated by IPLSm1 IgG2a antibodies. The blocking activity of IgG2c antibody was further demonstrated in vitro by the use of F(ab')2 fragments and in vivo by the inhibition of passively transferred immunity conferred by the IgG2a protective monoclonal antibody. These results indicate that blocking antibodies could play an important role in the expression of protective immunity during schistosome infection.
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PMID:Blocking activity of rat monoclonal antibodies in experimental schistosomiasis. 673 54

Two hybridomas secreting monoclonal IgM antibody to Schistosoma mansoni have been isolated following fusion of spleen cells from Balb/c mice immunized with living S. mansoni and NS1 myeloma cells. One monoclonal IgM antibody (WP66.4) mediated about the same level of passive protection against a challenge infection as immune serum from mice with a chronic S. mansoni infection. The other monoclonal antibody (WP66.2) did not give a significant level of passive protection. This result indicates that the effective monoclonal antibody recognizes an antigen which may be a valuable candidate for experimental vaccination. In vitro one monoclonal antibody (WP66.4) caused a much higher level of complement-dependent cytotoxicity than the other (WP66.2), suggesting a possible mechanism for the effect observed in vivo. With indirect immunofluorescence both monoclonal antibodies reacted with surface determinants on living S. mansoni schistosomula, adult worms and miracidia but these determinants were not detected on cercariae or lung schistosomula. Neither monoclonal antibody cross-reacted with S. haematobium schistosomula or Fasciola hepatica metacercariae, indicating a possible use for these reagents in differential diagnosis of S. mansoni infections.
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PMID:Passive immunization of mice against Schistosoma mansoni with an IgM monoclonal antibody. 706 56


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