Effect of endogenous and synthetic sex steroids on the clearance of antibody-coated cells.

Schreiber, AD; Nettl, F M; Sanders, MA; King, M; Szabolcs, P; Friedman, D.E; Gomez, Florie

doi:10.4049/jimmunol.141.9.2959

Cited by 47 publications

(2 citation statements)

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“…88 The effect of danazol may also be partially explained by it being a sex steroid analogue like progesterone, which can downregulate the expression of Fc receptors in monocytes, thereby decreasing immune-mediated clearance of platelets. 89,90 Recent studies revealed associations of clonal T-cell populations with CTP. Füreder and Fogarty reported the first two cases with clonal T-cell receptor (TCR) rearrangement.…”

Section: Thrombocytopenia-based Ctpmentioning

confidence: 99%

“…started a patient on danazol, potentially due to its ability to reduce oestrogen production, which resulted in a prolonged platelet response 88 . The effect of danazol may also be partially explained by it being a sex steroid analogue like progesterone, which can downregulate the expression of Fc receptors in monocytes, thereby decreasing immune‐mediated clearance of platelets 89,90 …”

Section: Underlying Pathogenic Elements Associated With Susceptibilit...mentioning

confidence: 99%

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The highs and lows of cyclic thrombocytopenia

Zhang,

Villar‐Prados,

Bussel

et al. 2023

Br J Haematol

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SummaryCyclic thrombocytopenia (CTP) is characterized by periodic platelet oscillation with substantial amplitude. Most CTP cases have a thrombocytopenic background and are often misdiagnosed as immune thrombocytopenia with erratically effective treatment choices. CTP also occurs during hydroxyurea treatment in patients with myeloproliferative diseases. While the aetiology of CTP remains uncertain, here we evaluate historical, theoretical and clinical findings to provide a framework for understanding CTP pathophysiology. CTP retains the intrinsic oscillatory factors defined by the homeostatic regulation of platelet count, presenting as reciprocal platelet/thrombopoietin oscillations and stable oscillation periodicity. Moreover, CTP patients possess pathogenic factors destabilizing the platelet homeostatic system thereby creating opportunities for external perturbations to initiate and sustain the exaggerated platelet oscillations. Beyond humoral and cell‐mediated autoimmunity, we propose recently uncovered germline and somatic genetic variants, such as those of MPL, STAT3 or DNMT3A, as pathogenic factors in thrombocytopenia‐related CTP. Likewise, the JAK2 V617F or BCR::ABL1 translocation that drives underlying myeloproliferative diseases may also play a pathogenic role in hydroxyurea‐induced CTP, where hydroxyurea treatment can serve as both a trigger and a pathogenic factor of platelet oscillation. Elucidating the pathogenic landscape of CTP provides an opportunity for targeted therapeutic approaches in the future.

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Section: Thrombocytopenia-based Ctpmentioning

confidence: 99%

Section: Underlying Pathogenic Elements Associated With Susceptibilit...mentioning

confidence: 99%

The highs and lows of cyclic thrombocytopenia

Zhang,

Villar‐Prados,

Bussel

et al. 2023

Br J Haematol

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Presence of estrogen‐binding sites on macrophage‐like synoviocytes and cd8+, cd29+, cd45ro+ t lymphocytes in normal and rheumatoid synovium

Cutolo

Accardo

Villaggio

et al. 1993

Arthritis & Rheumatism

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Objective. To study the presence of estrogenbinding sites (EBS) in the synovial tissues of male and female patients with rheumatoid arthritis (RA) and in age-and sex-matched healthy controls.Methods. Both type 1 (high affinity, low binding capacity) and type 2 (reduced affinity, higher binding capacity) EBS were investigated in both soluble and nuclear fractions of homogenized synovial tissue sam- ples by a dextran-coated charcoal method. To determine what type of synovial cell was positive for EBS, cryosections of synovial tissues were immunostained with a specific monoclonal anti-estrogen receptor antibody (anti-ER MAb) using both immunofluorescence and immunoperoxidase techniques. Double immunostaining with the anti-ER MAb and with specific MAb to detect different macrophage antigens (Ber-MAC3, MAC387, CD68) and CDS+ T cell subsets (CD29+, CD45RO+ and CD29-, CD45RO-) was performed.Results. Higher affinity EBS were found mostly in nuclear cell fractions of either RA or control synovial tissues (28 of the 33). These EBS were present to a lesser extent in soluble cell fractions (11 of the 33). Immunostaining showed the estrogen receptor-positive cells to be the macrophage-like synoviocytes and the CD8+, CD29+ T cells both in RA and in control synovial tissues. Higher nuclear content of EBS was consistent with more intense nuclear staining of synoviocytes and T cells.Conclusion. It is conceivable that the immunomodulatory activity exerted by estrogens is at least partly mediated through their interaction with EBS that are present on macrophage-like synoviocytes, functioning as antigen-processing and antigen-presenting cells, and on antigen-experienced (memory) CDS+ T lymphocytes (CD29+, CD45RO+).Females have better humoral immune responses and are more susceptible to autoimmune diseases than males. This sex-related dimorphism in immune capabilities is thought to be related to the physiologic effects of the sex hormones on the immune system (1-6). Generally, estrogens have immunostimulatory effects, whereas androgens are immunosup-

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Progesterone inhibits inducible nitric oxide synthase gene expression and nitric oxide production in murine macrophages

Miller¹,

Alley

Murphy³

et al. 1996

Journal of Leukocyte Biology

142

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The purpose of this study was to determine whether the female hormones estradiol-l7 beta (E2) and progesterone (P4) influence inducible nitric oxide synthase (iNOS) and the production of nitric oxide (NO) by interferon-gamma(IFN-gamma)-and lipopolysaccharide (LPS)-activated mouse macrophages. Treatment with P4 alone caused a time- and dose-dependent inhibition of NO production by macrophage cell lines (RAW 264.7, J774) and mouse bone marrow culture-derived macrophages as assessed by nitrite accumulation. RAW 264.7 cells transiently transfected with an iNOS gene promoter/luciferase reporter-gene construct that were stimulated with IFN-gamma/LPS in the presence of P4 displayed reduced luciferase activity and NO production. Analysis of RAW 264.7 cells by Northern blot hybridization revealed concurrent P4-mediated reduction in iNOS mRNA. These observations suggest that P4-mediated inhibition of NO may be an important gender-based difference within females and males that relates to macrophage-mediated host defense.

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Effect of endogenous and synthetic sex steroids on the clearance of antibody-coated cells.

Cited by 47 publications

References 0 publications

The highs and lows of cyclic thrombocytopenia

The highs and lows of cyclic thrombocytopenia

Presence of estrogen‐binding sites on macrophage‐like synoviocytes and cd8+, cd29+, cd45ro+ t lymphocytes in normal and rheumatoid synovium

Progesterone inhibits inducible nitric oxide synthase gene expression and nitric oxide production in murine macrophages

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