Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0220723 (PCA)
 4,687 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of eosinophil cationic protein (ECP) on immunoglobulin (Ig) production by and proliferation of human plasma cells was studied. ECP inhibited Ig production by and proliferation of the human plasma cell lines, IM-9 and AF-10, in a dose-dependent fashion. As little as 0.05 ng/ml ECP was found to be inhibitory, and the maximal inhibition was achieved at doses of 0.1-0.5 ng/ml ECP. This inhibition was not due to cytotoxicity, since viability was always greater than 98%. Kinetic experiments demonstrated that inhibition was observable after 24 hr of culture with ECP and that the inhibitory effect of ECP was reversible. The inhibitory effect of ECP could be blocked by anti-ECP serum, but not by control serum. Of the various cytokines tested, including interleukin (IL)-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, interferon (IFN)-alpha, IFN-gamma, granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (Epo), IL-6 reversed the inhibition, while other cytokines failed to do so. ECP also inhibited Ig (IgG1, IgG2, IgG3, IgG4, IgM, and IgA) production by and proliferation of PCA-1+ plasma cells generated in vitro with a similar dose-response pattern. This inhibition also was blocked by anti-ECP serum but not by control serum, and was restored by IL-6. These results suggest that ECP may interact with IL-6 in controlling plasma cell responses.
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PMID:Eosinophil cationic protein inhibits immunoglobulin production and proliferation in vitro in human plasma cells. 157 57

The effect of recombinant human erythropoietin (Epo) on plasma cells was studied in a serum-free medium, COSMEDIUM-001 (Cosmedium). Epo enhanced both Ig production and thymidine uptake by human plasma cell lines, AF-10 and IM-9. Interleukin-6 (IL-6) enhanced both Ig production and thymidine uptake by AF-10 and IM-9, while other cytokines, including IL-1 beta, IL-2, IL-3, IL-4, IL-5, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-alpha (IFN-alpha) or IFN-gamma, failed to do so. However, the Epo effect was specific since Epo-induced enhancement of Ig production and thymidine uptake was blocked by the anti-Epo antibody but not by the anti-IL-6 antibody or the control antibody. Conversely, IL-6-induced enhancement was blocked by the anti-IL-6 antibody but not by the anti-Epo antibody. Epo also enhanced Ig production (IgG, IgM, and IgA) and thymidine uptake by PCA-1+ plasma cells generated in vitro. This enhancement was also blocked by the anti-Epo antibody but not by the anti-IL-6 antibody. Taken together, these results suggest that Epo enhances plasma cell responses by a different mechanism than does IL-6.
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PMID:Erythropoietin enhances immunoglobulin production and proliferation by human plasma cells in a serum-free medium. 202 98

The effect of mitogens and/or recombinant B-cell growth factors (M/GFs) on the in vitro growth of hairy cells was examined. Tumor cells were isolated from the spleens of four patients with hairy cell leukemia (HCL) by Ficoll-Hypaque sedimentation and E-rosetting. Enrichment for tumor cells was confirmed with intracytoplasmic immunoglobulin (Ig) staining, tartrate resistant acid phosphatase (TRAP) staining, and staining using monoclonal antibodies (MoAbs) directed at B, T, myeloid, and monocytoid antigens (Ags) in indirect immunofluorescence assays. Tumor cells were B1(CD20)+ B2(CD21)- B4(CD19)+ IL-2R(CD25)+ PCA-1 +/- TRAP+. HCLs neither synthesized DNA nor secreted Ig in response to culture with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL-3, IL-4, IL-5, or IL-6. However, a proliferative response (stimulation index greater than or equal to 3.0) without Ig secretion was triggered in HCLs by mitogens or combinations of GFs. Specifically, DNA synthesis was induced at 3 days in three of four HCL samples cultured with Staphylococcus aureus Cowan A (SAC) or the combination of phorbol ester (TPA) and the calcium ionophore A 23187 (Ca2+); DNA synthesis was triggered later (day 7) by tumor necrosis factor (TNF) or by IL-4 and IL-5. In contrast, the fourth patient, a nonresponder to SAC or TPA/Ca2+, demonstrated increased DNA synthesis at day 3 when cocultured with IL-4 and IL-5. Both autoradiography and staining with antibromodeoxyuridine (BrdU) MoAb conjugated to fluorescein confirmed DNA synthesis by only a minority (5% to 23%) of tumor cells within each patient. Dual staining confirmed that responsive cells were both BrdU+ and TRAP+. DNA synthesis induced by TPA/Ca2+ was blocked specifically by anti-IL-6 Ab; in contrast, the HCL proliferative response to SAC, TNF, or IL-4 and IL-5 was not inhibited by anti-IL-6 Ab. alpha-Interferon inhibited the response to TPA/Ca2+, TNF, or IL-4 and IL-5 without any effect on response to SAC. Finally, peroxidase-antiperoxidase staining demonstrated that HCLs are induced by TPA/Ca2+, but not by SAC, to produce intracytoplasmic IL-6. These data demonstrate IL-4, IL-5, and IL-6 mediated DNA synthesis by HCLs in vitro and suggest a possible in vivo role for these growth factors in the pathophysiology of HCL.
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PMID:Response patterns of hairy cell leukemia to B-cell mitogens and growth factors. 224 29

A number of antigens (Ags) are expressed on normal and malignant terminal B (plasma) cells, including plasma-cell, earlier B-cell, and non-B cell-Ags. These Ags, coupled with indirect and dual fluorochrome labelling techniques, permit characterization of normal and malignant in vitro and in vivo terminal B-cell differentiation. The majority (90%) of B cells within spleen bear Bl and lack PCA-1 Ags. As B cells differentiate to pokeweed mitogen in vitro, immunoglobulin (Ig) secretion precedes the appearance of cell surface PCA-1 and plasmacytoid morphology. Dual fluorescence cell sorting permits characterization of in vivo B-cell differentiation: Bl + PCA-1 + cells are more "differentiated" since they are more prevalent in lymph node than spleen, exhibit plasmacytoid morphology and maximal Ig secretion, and no longer respond to triggers of B-cell proliferation; in contrast, Bl + PCA-1-cells are lymphoid in morphology and may respond to triggers of B-cell proliferation as "resting" B cells. Similar studies of myeloma cells demonstrated that they may also include cells expressing plasma-cell, earlier B, and non-B cell Ags. Although they neither proliferated nor secreted Ig in vitro to G/M-CSF, G-CSF, M-CSF, IL-1, IL-1B, IL-2, or IL-4, proliferation without Ig secretion (Stimulation Index greater than or equal to 3.0) was induced to IL-6 in 6 of 10 patients (pts); to IL-3 (2 pts) and to IL-5 (2 pts).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phenotypic and functional characterization of normal and malignant terminal B (plasma) cells. 262 90

The discovery of anaphylaxis by Portier and Richet that reinjection of a substance caused disease instead of immunity was sensational as it was against the prevailing DOGMA. Passive transmission of hypersensitivity with human antibody by Prausnitz (the P-K reaction, 1921) was an important step in the study of human hypersensitivity. Anaphylaxis was shown to be the consequence of liberation of vasoactive substances (histamine and SRS-A) from mast cells when the allergen crosslinks two IgE molecules fixed to mast cell Ig receptors (Ovary, 1961). The use of smooth muscle contraction (Dale, 1913) and vascular permeability increase (PCA, Ovary, 1948) became important for experimental studies. The clonal selection of antibody formation (Burnet, 1929) opened a new era in immunological concepts. The demonstration of the Fc receptor on mast cells (Ovary, 1961) called attention to the importance of cellular receptors. The carrier effect (Ovary & Benacerraf, 1963) was explained by recognition by T cell receptors of a processed carrier fragment complexed to Ia molecules (Unanue, Grey, 1981). Human IgE responsible for allergies was discovered in 1965 by K. & T. Ishizaka. Tonegawa in 1973 destroyed the "one gene-one protein" DOGMA, showing that the immunoglobulin, germline gene is discontinuous: i.e., composed of exons (which will form the Ig molecule) separated by introns. The CD4 cells were subdivided into Th1 and Th2 cells (Mosmann & Coffman, late 1980's). The Th2 secretes IL-4 necessary for IgE production (Paul, Vitetta, & others, early 1980's). B cells multiply before antibody production or become memory B cells, but what causes a B cell to become a memory cell is not known. The B cell does not change specificity but can switch the isotype using "switch recombinase" and the s segment of the Ig molecules (Honjo, early 1980's). IgE production was shown to be suppressed by lymphokines, such as IFN-gamma and IL-2. A great progress in understanding the mechanism of allergic reaction has been the result of intense investigations by many scientists. A more complete understanding, better prophylaxis and an improved treatment are the goals of the near future.
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PMID:Immediate hypersensitivity. A brief, personal history. 769 78

In contrast to several inbred strains of mice that develop Th1-associated anticandidal protection, DBA/2 mice are highly susceptible to systemic infection with Candida albicans cells of the attenuated variant PCA-2, and fatal outcome is observed in concurrence with sustained CD4+ cell production in vitro of IL-4 and IL-10. These Th2 cytokines were previously shown to inhibit nitric oxide (NO) production and yeast killing by activated macrophage cultures. We now show that macrophages from DBA/2 mice, either intact or infected with PCA-2, have lower capacity than resistant strains to synthesize NO in response to IFN-gamma. However, when treated with anti-IL-10 Abs at the time of infection, DBA/2 mice survived challenge and displayed increased production of NO in vitro after IFN-gamma activation. Cure was associated with the onset of footpad responses and durable protection, and higher frequencies of IFN-gamma-secreting cells were found in splenic CD4+ lymphocytes that expressed lower levels of IL-4 and IL-10 mRNA. Therefore, in DBA/2 mice, IL-10 contributes significantly to the selection of a Th2 response and lethality after PCA-2 challenge. An IL-10-induced defect in the activation and/or expansion of IFN-gamma-producing Th1 cells, IL-10 suppression of yeast killing, and the relative inability of DBA/2 macrophages to produce adequate levels of candidacidal NO may all contribute to the abnormal susceptibility of these mice to candidiasis.
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PMID:Neutralization of IL-10 up-regulates nitric oxide production and protects susceptible mice from challenge with Candida albicans. 790 4

By means of polymerase chain reaction-assisted mRNA amplification, we have monitored message levels of interleukin (IL)-12 in splenic macrophages and of interferon-gamma (IFN-gamma), IL-4, and IL-10 in CD4+ and CD8+ T cells using Candida albicans/host combinations that result either in a T helper type-1 (Th1)-associated self-limiting infection ("healer mice") or in a Th2-associated progressive disease ("nonhealer mice"). The timing and pattern of message detection did not differ qualitatively by the expression of IFN-gamma or IL-10 mRNA in CD4+ and CD8+ cells from healer (i.e. PCA-2 into CD2F1) vs. nonhealer (i.e. CA-6 into CD2F1 or PCA-2 into DBA/2) mice. In contrast, IL-4 mRNA was uniquely expressed by CD4+ cells from nonhealer animals. IL-12p40 was readily detected in macrophages from healer mice but was detected only early in infection in mice with progressive disease. Cytokine levels were measured in sera, and antigen-driven cytokine production by CD4+ and CD8+ cells was assessed in vitro, while IFN-gamma-producing cells were enumerated in CD4- CD8- cell fractions. Overall, our results showed that (i) antigen-specific secretion of IFN-gamma protein in vitro by CD4+ cells occurred only in healing infection; (ii) IL-4- and IL-10-producing CD4+ cells would expand in nonhealer mice in the face of high levels of circulating IFN-gamma, likely released by CD4- CD8- lymphocytes; (iii) a finely regulated IFN-gamma production correlated in the healer mice with IL-12 mRNA detection, and IL-12 was required in vitro for yeast-induced development of IFN-gamma-producing CD4+ cells. Although the mutually exclusive production of IL-4/IL-10 and IFN-gamma by early CD4+ cells may be the major discriminative factor of cure and noncure responses in candidiasis, IL-12 rather than IFN-gamma production may be an indicator of Th1 differentiation.
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PMID:Interleukin-12 but not interferon-gamma production correlates with induction of T helper type-1 phenotype in murine candidiasis. 790 34

Interleukin-6 (IL-6) is the major cytokine to date mediating antigen (Ag)- or mitogen-driven B cell differentiation. Recently, CD40 ligand (CD40L), with the co-stimulatory cytokines IL-4 and IL-10, has been shown to trigger immunoglobulin (Ig) secretion and class switching. In the present report, we have examined the role of IL-6 in mediating B cell differentiation and Ig secretion triggered with CD40L and/or these cytokines. Culture of splenic B cells with CD40L triggered (1) significant (5.4-fold) increases in IL-6 secretion; (2) differentiation, evidenced by sequential loss of B cell (CD20, CD21) and acquisition of plasma cell (CD38, PCA-1) surface antigens (Ags); and (3) Ig secretion. Interleukin-4 increased both IL-6 and IgG secretion stimulated by CD40L. Interleukin-10+ CD40L triggered 100-fold increments in IgG, IgA and IgM secretion, but IL-10 suppressed IL-6 secretion triggered with CD40L +/- IL-4. Exogenous IL-6 can further increase IgG secretion induced by CD40L + IL-10; moreover, the anti-IL-6 monoclonal antibody partially blocked IgG secretion triggered by CD40L +/- IL-4 or IL-10. Finally, IL-10 suppressed differentiation of B cells induced by CD40L. These studies suggest that CD40L augments Ig secretion in at least two mechanisms: by triggering IL-6 secretion and related differentiation, and by priming B cells for responsiveness to IL-10.
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PMID:CD40 ligand triggers interleukin-6 mediated B cell differentiation. 870 23

Various side effects have been associated with the clinical use of contrast media. Immunological mechanisms have been proposed but there have been very few experimental studies with animal models. We have attempted to develop murine models to determine whether or not anaphylactic antibodies such as IgE and IgG1 against hapten (DNP) were enhanced with contrast medium (iopamidol) as an adjuvant or if the contrast medium itself produced antibodies of the IgE class. The results showed that anti-hapten IgE and IgG1 production was greatly enhanced with immunogen plus contrast medium. Anti-contrast medium antibodies of the IgE class could not be detected by PCA reactions. The enhancement of IgE and IgG1 production for hapten was associated with IL-4 release by the neutralization test used by monoclonal anti-IL-4 antibodies. This is the first observation to show that contrast media may have a strong adjuvant effect for the production of IgE and IgG1. This murine model demonstrates a possible immunological function of contrast media in vivo.
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PMID:Anaphylactic IgE and IgG1 production for hapten can be enhanced by contrast media. 903 27

Due to its dependence on IL-4 and IL-13 production, IgE production is frequently used to assess the type 2 character of an immune effector response. It is particularly relevant to measure IgE in murine models of immediate hypersensitivity, as allergen specific IgE is a critical effector molecule in this process. Given the complexity of developing ELISAs to measure specific IgE, total IgE levels are often reported with the implicit assumption that this provides an accurate gauge of specific IgE responses. Here, we rigorously test this assumption by examining the relationship between total and Ag-specific IgE levels in mice immunized to elicit a wide range of serum IgE responses. We identify a strong, consistent relationship between total and Ag-specific IgE, regardless of the phenotype of the immune response (type 1 vs. type 2 biased), the nature of the immune response (primary vs. recall), the genetic background of mouse strain examined (C57Bl/6, BALB/c or outbred CD1 mice), or the intensity of the initial immunological stimulus (0.2, 2.0 or 100 microg OVA). These findings indicate that measurement of total IgE levels through straightforward, easy to develop, total IgE ELISAs offers an appropriate surrogate for measurement of Ag-specific IgE levels, usually measured through the use of subjective PCA assays or Ag-specific IgE ELISAs.
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PMID:In vivo IgE levels in exogenous antigen stimulated responses: measurement of total IgE as a valid, simple surrogate for Ag-specific IgE. 1508 27


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