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

Four human myeloma cell lines (MM-S1, MM-A1, MM-Y1 and MM-C1) were established from patients in the terminal stage of multiple myeloma. All the cell lines were PCA-1 positive and three were CD38 (OKT10) positive. The class of cytoplasmic immunoglobulin in each of these cell lines was identical to that of the monoclonal protein detected in each patient. Epstein-Barr virus nuclear antigen was negative in all cell lines. An examination of the tritiated thymidine uptake showed that all four cell lines proliferated in response to interleukin-6 (IL-6), while MM-S1 also responded to IL-5. Immunological staining with an anti-IL-6 receptor monoclonal antibody revealed the presence of receptors for IL-6 on the cells from each cell line. Three of them formed colonies dependent on IL-6 in methylcellulose semi-solid culture. All four cell lines grew better when human plasma was added as a supplement to the culture in comparison to fetal calf serum. Northern blot analysis showed that the three cell lines tested did not express IL-6 messenger RNA. These results indicate that these four cell lines are responsive to IL-6, but not by an autocrine mechanism, at least in the three lines examined.
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PMID:Establishment and characterization of four myeloma cell lines which are responsive to interleukin-6 for their growth. 207 43

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

We performed general and topical sensitization by ovalbumin in wild type, WBBFI6- +/+ (+/+), mice and mast cell-depleted type, WBBFI6-W/Wv (W/W)v, mice. Although both mice showed almost equal PCA liters, W/Wv mice showed a lower level of antigen-induced eosinophilia, and more significant nasal symptoms and histamine hypersensitivity than +/+ mice. Antigen-induced increased levels of histamine and IL-5 in nasal lavage fluid were noted in +/+ mice. Cyclosporin A pre-treatment inhibited the antigen-induced nasal symptoms, nasal eosinophilia and increased levels of histamine and IL-5 in nasal lavage fluid in the +/+ mice. The PCA titer was not affected by the treatment in either kind of mouse.
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PMID:[Manifestation of nasal allergy in ovalbumin-sensitized mice--as compared with mast cell-deficient mice, determined with an immunosuppressive agent]. 893 80