M Plaut

National Institutes of Health, 베서스다, Maryland, United States

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Publications (60)455.91 Total impact


    No preview · Article · Dec 2006 · Annals of the New York Academy of Sciences
  • William E. Paul · Robert A. Seder · Marshall Plaut
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    ABSTRACT: This chapter discusses the growing information on production of interleukin-4 (IL-4) and of a set of related lymphokines, such as IL-3, IL-5, and granulocyte–macrophage colony-stimulating factor (GM-CSF) by mast cells and other FcɛRI+ cells as well as production of tumor necrosis factor (TNF-α), IL-6, IL-1, and IL-8 and its congeners by these cells. It discusses the pathophysiologic conditions in which lymphokine production by FcɛRI+ cells is increased and the signaling mechanisms employed by FcɛRI+ cells that lead to lymphokine production. Lymphokines and cytokines mediate a wide range of biologic functions. They are responsible for much of the regulatory activity of T cells and have potent pro- and anti-inflammatory properties. Mast cells and basophils are cell types that have two major phenotypic properties in common. They both store histamine and both express high-affinity FcɛR, called FcɛRI. The chapter establishes that transformed mast cells, factor dependent mast cells, and freshly isolated FcɛRI+ cells all have the capacity to produce lymphokines and cytokines. In particular, the set of molecules produced by these cells, including IL-4, IL-3, GM-CSF, and IL-5, as well as IL-1, IL-6, TNF-a, and IL-8, have very important roles in the regulation of inflammatory responses. It is particularly striking that the lymphokines produced have potential roles in immunologically important responses, most notably in orchestrating the events associated with allergic inflammation.
    No preview · Article · Dec 1993 · Advances in Immunology
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    ABSTRACT: Previous work showed that injection of mice with goat anti-mouse IgD antibodies results in increased numbers of Fc epsilon R-positive, non-B, non-T cells in the spleen and Fc epsilon R-positive cells in the bone marrow, and that some of these cells had ultrastructural features of basophils. Fc epsilon R-positive, non-B, non-T cells express virtually all of the capacity of mouse splenic "non-B, non-T cells" to produce interleukin-4 in response to stimulation by cross-linking of Fc epsilon R or Fc gamma R, or by the calcium ionophore, ionomycin. The present study is a detailed ultrastructural analysis of Fc epsilon R-positive bone marrow cells or Fc epsilon R-positive splenic non-B, non-T cells sorted from mice injected with goat anti-mouse IgD antibody and of Fc epsilon R-positive bone marrow cells or spleen cells pooled from normal mice not injected with goat anti-IgD. Basophils represented the majority (90%) of the granulated cells present in the Fc epsilon R-positive splenic non-B, non-T cells or Fc epsilon R-positive bone marrow cells of goat anti-IgD-injected mice. In contrast, the cytoplasmic granule-containing Fc epsilon R-negative cells sorted from spleen or bone marrow of goat anti-IgD-injected animals contained predominantly a mixture of neutrophils, eosinophils, monocytes and their precursors. Both the Fc epsilon R-positive and -negative preparations contained rare (< 5%) cells with ultrastructural features of very immature mast cells. Basophils were also identified in Fc epsilon R-positive cells sorted from total bone marrow cells or spleen cells of normal mice not injected with goat anti-IgD. Taken together with data concerning the numbers of Fc epsilon R-positive, non-B, non-T cells in the spleen, and Fc epsilon R-positive B220-negative cells in the bone marrow, these ultrastructural findings indicate that injection of mice with goat anti-IgD results in increased numbers of basophils, particularly in the spleen, that exhibit an 8-fold increase in basophils as a result of injection of goat anti-IgD.
    No preview · Article · Jul 1993 · Laboratory Investigation
  • Marshall Plaut

    No preview · Article · Jul 1993 · Annals of the New York Academy of Sciences
  • W E Paul · R A Seder · M Plaut

    No preview · Article · Feb 1993 · Advances in Immunology
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    A D Keegan · J H Pierce · J Artrip · M Plaut · W E Paul
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    ABSTRACT: IL-3 dependent mast cell lines produce cytokines in response to Fc receptor cross-linkage or to ionomycin. In this study we have observed that cells pre-cultured in IL-3 produce 10-100 times more cytokine after receptor cross-linkage in comparison with IL-4 pre-cultured cells. Although several hematopoietin receptors, including those for IL-3, IL-4 and EPO, do not contain tyrosine kinase domains, their occupancy with ligand causes tyrosine phosphorylation of specific cellular substrates. Therefore, the contribution of tyrosine kinase activation to the ability of an IL-3 dependent mast cell line, CFTL-15, to produce cytokines was analyzed. The CFTL-15 cells were transfected with growth factor receptors containing ligand-inducible tyrosine kinase domains (EGFR and PDGFR, and CSF-IR) or with the EPOR. All of the transfectants were able to proliferate in response to IL-3 or to their respective growth factor and to produce IL-3 in response to IgE receptor cross-linkage. Stimulation of the EGFR and PDGFR transfectants with their respective ligands resulted in the production of IL-3, IL-6, and GM-CSF. Stimulation of the CSF-1R or EPOR transfectants with growth factor alone failed to induce cytokine production. However, in co-stimulation assays each of the growth factors enhanced the amount of cytokine produced in response to Fc epsilon RI cross-linkage. The ability of these stimuli to induce tyrosine phosphorylation in the transfectants was analyzed. Fc epsilon RI cross-linkage in the transfectants routinely induced the tyrosine phosphorylation of 145, 86 and 72 kDa proteins, with occasional phosphorylation of 55, 52, and 40 kDa proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
    Full-text · Article · Jan 1992 · The EMBO Journal
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    ABSTRACT: Non-B, non-T cells from spleen and bone marrow cells produce IL-4 in response to cross-linkage of high affinity receptors for Fc epsilon R or Fc gamma RII, and to treatment with calcium ionophores. Cells bearing high affinity Fc epsilon R constituted 1 to 2% of non-B, non-T cells of spleen and of total bone marrow cells from naive donors. In mice whose immune systems had been polyclonally activated by injection with anti-IgD antibodies or had been infected with Nippostrongylus brasiliensis larvae, the frequency of Fc epsilon R+ cells in splenic non-B, non-T cells was also 1 to 2% but in bone marrow from anti-IgD-injected mice donors the frequency was approximately 5%. Cell sorting experiments revealed that all of the capacity to produce IL-4 in response to immobilized IgE or IgG2a or to ionomycin was found in the Fc epsilon R+ fraction. Among the Fc epsilon R+ spleen cells from naive donors, the frequency of IL-4-producing cells was 1/20 to 1/40 whereas in mice that had been injected with anti-IgD or infected with N. brasiliensis, the frequency of IL-4 producing cells in the Fc epsilon R+ population was approximately 1/5.
    No preview · Article · Sep 1991 · The Journal of Immunology
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    ABSTRACT: Splenic and bone marrow cells from normal mice, and from mice that have been polyclonally activated by injection of anti-IgD antibody, contain cells that produce interleukin 4 (IL-4) in response to crosslinkage of Fc epsilon receptors (Fc epsilon R) or Fc gamma R or to ionomycin. Isolated Fc epsilon R+ cells have recently been shown to contain all of the IL-4-producing capacity of the nonlymphoid compartment of spleen and bone marrow. Here, purified Fc epsilon R+ cells are shown to be enriched in cells that contain histamine and express alcian blue-positive cytoplasmic granules. By electron microscopy, the vast majority of cytoplasmic granule-containing cells are basophils; they constitute approximately 25% and approximately 50%, respectively, of Fc epsilon R+ spleen and bone marrow cells from anti-IgD-injected mice. The Fc epsilon R- populations contain cells that form colonies typical of mast cells. The Fc epsilon R+ populations also contain cells that, upon culture with IL-3, form colonies of alcian blue-positive cells, but (in contrast to colonies derived from Fc epsilon R- populations) the colonies are small, and all the cells die within 2-3 weeks. The Fc epsilon R+ cells synthesize histamine during a 60-hr culture with IL-3, while the Fc epsilon R- cells do not. These results indicate that IL-4-producing Fc epsilon R+ cells are highly enriched in basophils.
    Preview · Article · May 1991 · Proceedings of the National Academy of Sciences
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    ABSTRACT: Interleukin-3 (IL-3)-dependent mast cell lines, upon stimulation by calcium ionophores or by Fc epsilon RI cross-linking, express mRNA for, and secrete, a distinct pattern of cytokines, similar to those secreted by cloned mouse T cells of the TH2 type. The mast-cell-derived cytokines include IL-3, IL-4, IL-5 and IL-6. Not only in vitro mast cell lines, but also in vivo derived peritoneal mast cells secrete cytokines. An in vivo derived cell, in mouse spleen and bone marrow, secretes IL-4 and other cytokines upon stimulation with calcium ionophores or by Fc epsilon RI cross-linking or Fc gamma RII cross-linking. The IL-4-producing cells are highly enriched in the Fc epsilon R+ subset of spleen and bone marrow cells. These Fc epsilon R+ cells produce large amounts of IL-4, and they have characteristics similar to those of immature mast cells and/or basophils. It is possible that cytokines produced by mast cells and/or basophils participate in allergic inflammatory diseases.
    No preview · Article · Feb 1991 · International archives of allergy and applied immunology
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    ABSTRACT: A spleen cell population that lacks CD3, CD4, CD8, Thy-1, B220, and class II major histocompatibility complex cell-surface markers (non-B, non-T cells) produces IL-4 when cultured in wells coated with IgE. Their production of IL-4 in response to plate-bound (PB)-IgE is strikingly enhanced by IL-3, and in the presence of IL-3, these cells also produce IL-4 in response to PB-IgG2a. The effect of IL-3 is not mimicked by IL-1, IL-2, IL-5, IL-6, IL-7, granulocyte-macrophage CSF (GM-CSF) or IFN-gamma. Non-B, non-T cells cultured with IL-3 for 12 h acquire the capacity to produce enhanced amounts of IL-4 in response to subsequent culture with PB-Ig even if IL-3 is omitted from the second culture. Irradiated cells also respond to IL-3 with enhanced capacity to produce IL-4 to PB-Ig, indicating that cell proliferation is not required for the effect of IL-3. The IL-3 effect can be obtained in vivo; treatment of mice with a total dose 90,000 U of synthetic IL-3 over a 3-day period results in the presence of splenic and peritoneal cavity non-B, non-T cells that produce enhanced amounts of IL-4 in response to PB-Ig. The FcR that mediates the response to PB-IgE appears to be Fc epsilon RI because cells can be sensitized with IgE anti-DNP mAb, washed, cultured for 15 h at 37 degrees C, washed again, and stimulated to produce IL-4 with 0.1 to 1 ng/ml of TNP10-OVA. IL-3 does not appear to mediate its function by increasing the number of Fc epsilon RI because it can exert its effect when cultured with non-B, non-T cells after they have been sensitized with IgE anti-DNP. However, IL-3 pretreatment does affect the signaling process in that non-B, non-T cells sensitized with IgE anti-DNP show strikingly reduced production of IL-4 to concentrations of TNP10-OVA of 100 ng/ml or more whereas cells pretreated with IL-3 show little or no diminution in IL-4 production at concentrations of TNP10-OVA up to 1 microgram/ml.
    No preview · Article · Nov 1990 · The Journal of Immunology
  • M Plaut

    No preview · Article · Jul 1990 · The Journal of Immunology
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    ABSTRACT: We have analyzed the effects of overnight culture of human basophils with a variety of cytokines in the presence or absence of the glucocorticoid dexamethasone. The 24-h culture of basophils with a range of concentrations of several cytokines (granulocyte-macrophage-CSF, TNF-alpha, IL-1, IL-2, and IL-4) had no effect either on anti-IgE-induced histamine release or the inhibitory effects of dexamethasone on histamine release. IFN-gamma enhanced postculture releasability of human basophils. The concentration range for this effect was from 50 to 50,000 U/ml and maximal enhancement of anti-IgE-induced basophil histamine release was approximately 200% of control. IFN-gamma did not increase the number of occupied or unoccupied Fc epsilon RI on human basophils, suggesting that the enhancement of histamine release is a result of an intrinsic increase in the releasability mechanism. rIL-3 also augmented basophil releasability (approximately 250% of control) by a mechanism independent of alterations in basophil cell surface IgE density. The increase in post culture releasability occurred in both partially purified basophils (12 to 90% purity) and mixed leukocytes (approximately 1% basophils) although it was more marked in the former. Enhanced postculture releasability after exposure to IL-3 occurred for both IgE-dependent (anti-IgE) and peptide-mediated (fmet-leu-phe) responses and included elevations in the release of both histamine and sulfidopeptide leukotriene, suggesting a global increase in releasability. Basophils cultured in the presence of IL-3 were insensitive to the inhibitory effects of dexamethasone; at 1,000 U/ml IL-3, dexamethasone inhibition of basophil mediator release was completely blocked. None of the other cytokines tested, with the exception of crude or partially purified IL-2 preparations, had this effect. IL-3 contamination may explain the ability of these partially purified "IL-2" preparations to block the inhibitory effects of dexamethasone, because this effect was abolished by a specific anti-IL-3 antibody. These results suggest that IFN-gamma and IL-3 may modulate the response of human basophils in allergic reactions. Furthermore, increased local production of IL-3 may "prime" basophils for increased releasability and override inhibitory effects of elevated systemic glucocorticoids on human basophils. Finally, we conclude that the effects of glucocorticoids on human basophils may be in part mediated indirectly by effects on cells which produce cytokines, such as IFN-gamma and IL-3, that can modulate basophil function.
    No preview · Article · Sep 1989 · The Journal of Immunology
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    ABSTRACT: The cross-linkage of high affinity Fc epsilon receptors (Fc epsilon RI) on mast cells and basophils is central to the induction of allergic inflammatory responses. As a result of such cross-linkage, mast cells secrete a variety of preformed biologically active substances, such as histamine, and newly synthesized arachidonic acid metabolites. Here we show that cross-linkage of Fc epsilon RI on a series of nontransformed murine mast cell lines, or treatment of these cells with calcium ionophores, stimulates increased messenger RNA levels and secretion of a group of lymphokines classically produced by a subset of murine T cell lines (TH2 cells). These factors include interleukin-3 (a mast cell growth factor)s interleukin-4 (an IgE 'switch factor'), interleukin-5 (an eosinophil differentiation factor) and interleukin-6 (a factor controlling immunoglobulin secretion). The production of these polypeptide factors by mast cells may have great importance in the induction of allergic and anti-parasite inflammatory responses.
    No preview · Article · Jun 1989 · Nature
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    ABSTRACT: With a skin blister technique in which the mediators generated by the trauma of forming the blister are allowed to subside, we have collected human interstitial skin fluid during the course of allergic reactions to ragweed, and measured levels of histamine and prostaglandin D2 (PGD2). Of 18 ragweed-allergic individuals tested, 11 developed both an immediate and a late-phase reaction (LPR) with fivefold-elevated levels of histamine (40 ng/ml) at 30 minutes and a peak level of PGD2 (6.5 ng/ml) later at 2 1/2 hours after ragweed challenge. The other seven allergic individuals had immediate reactions without an LPR lesion and demonstrated somewhat smaller elevations of histamine (25 ng/ml) but much lower levels of PGD2 (1.6 ng/ml; p less than 0.05). The time course of appearance of these mediators was identical in both groups of patients. The fluids from unchallenged blisters of allergic and nonallergic patients and the fluids of nonallergic patients challenged with ragweed had similar levels of histamine, at the lower limit of detection, and undetectable PGD2 levels. The peak levels of PGD2 in allergic individuals correlated with the size of the LPR lesion (p less than 0.05). These data suggest that the LPR involves the secondary elaboration of mediators different from mediators responsible for the immediate manifestations of the allergic skin reaction.
    No preview · Article · Aug 1988 · Journal of Allergy and Clinical Immunology
  • M Plaut · R P Schleimer
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    ABSTRACT: In this paper, we will not discuss all hormones, but will focus on the effects on murine anti-alloantigenic CTL of glucocorticoids and of histamine and other hormones that increase intracellular levels of cAMP.
    No preview · Article · Feb 1988 · Annals of the New York Academy of Sciences

  • No preview · Article · Jan 1988 · Journal of Allergy and Clinical Immunology
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    ABSTRACT: Crucial to the development of inflammatory infiltrates is the localized production of mediators which promote adherence of leukocytes to the vascular endothelium. Previous in vitro studies, using monolayers of cultured human vascular endothelial cells (VEC), have identified various agents which promote the acquisition of adhesiveness in VEC for polymorphonuclear leukocytes. In the present studies, we report that human lung fragments cultured for 4 to 24 hr release a factor which acts on VEC to promote adherence of polymorphonuclear leukocytes. Adhesiveness in VEC stimulated by lung fragment culture supernatants was time- and dose-dependent. This adherence-promoting factor appears to be a mixture of the alpha and beta forms of interleukin 1 (IL-1) and has the following properties: 1) it is heat-labile; 2) it is not inactivated by polymyxin B; 3) it has mobility on Sephadex G-75 column chromatography corresponding to apparent m.w. of approximately 15,000, 30,000, and 70,000 (a pattern observed previously for IL-1); 4) it has activity in the thymocyte costimulation IL-1 assay, but no interleukin 2 activity, and 5) it is neutralized by anti-human IL-1 antisera but not by anti-human tumor necrosis factor antiserum. Production and release of IL-1 in vivo may play a role in the development of inflammatory infiltrates in human lung and other tissues by acting on endothelium to promote the localized adherence of leukocytes.
    No preview · Article · Nov 1987 · The Journal of Immunology
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    ABSTRACT: Nasal lavage fluids from unstimulated individuals contain a histamine-releasing factor (HRF) similar to those which we have previously described from macrophages, platelets, and from blister fluids obtained during the late cutaneous reaction. The nasal HRF was partially purified by ion-exchange chromatography and gel filtration. Although some m.w. heterogeneity was observed, the majority of the HRF eluted at an apparent m.w. range of 15,000 to 30,000. This partially purified HRF induced histamine release from basophils of certain individuals. Histamine release occurred via a mechanism which is IgE-dependent in that: basophils desensitized by exposure to anti-IgE in the absence of calcium no longer respond to HRF, and desensitization with HRF reduces responsiveness to anti-IgE; and removal of IgE from the basophil surface by using lactic acid renders cells unresponsive to HRF. We have further defined this IgE dependence and have shown that the reason that only selected basophil donors respond to HRF is due to a previously unrecognized, functional heterogeneity of IgE. Thus, passive sensitization using sera from responders restored the responsiveness of acid-stripped basophils and conferred responsiveness to basophils of a nonresponder with naturally unoccupied IgE receptors. Sera from nonresponders failed to do this even though similar numbers of IgE molecules were put onto the basophil surface in each case. This property of responder sera was due to IgE because both heating sera at 56 degrees C for 2 hr and passage of sera over anti-IgE-Sepharose (which removes greater than 90% of the IgE) markedly reduced the ability of sera to induce responsiveness, and because an excess of either purified IgE myeloma or purified penicillin-specific IgE antibody from a nonresponder competitively inhibited the ability of IgE from responder sera to induce responsiveness to HRF. We conclude that nasal lavage fluids contain an HRF which induces basophil histamine release in a specific, IgE-dependent fashion but only from individuals with the appropriate type of IgE. Because we have shown that basophils are recruited into the nose during the late-phase reaction, we suggest that nasal HRF may induce these cells to release histamine and other mediators which could contribute to the symptomatology of the late-phase reaction.
    No preview · Article · Aug 1987 · The Journal of Immunology
  • M Plaut

    No preview · Article · Feb 1987 · Annual Review of Immunology

  • No preview · Article · Dec 1986 · Journal of Allergy and Clinical Immunology

Publication Stats

4k Citations
455.91 Total Impact Points


  • 1993
    • National Institutes of Health
      • Laboratory of Immunology
      베서스다, Maryland, United States
  • 1990-1993
    • National Institute of Allergy and Infectious Diseases
      • Laboratory of Parasitic Diseases (LPD)
      베서스다, Maryland, United States
  • 1973-1992
    • Johns Hopkins University
      • Department of Medicine
      Baltimore, Maryland, United States
  • 1985-1989
    • Good Samaritan Hospital
      Cincinnati, Ohio, United States
  • 1986
    • University of Texas Medical Branch at Galveston
      • School of Medicine
      Galveston, Texas, United States
  • 1980
    • Johns Hopkins Medicine
      Baltimore, Maryland, United States