Activation of stimulus-specific serine esterases (proteases) in the initiation of platelet secretion. I. Demonstration with organophosphorus inhibitors.

Henson, Peter M.; Gould, Doug W; Becker, Elmer L.

doi:10.1084/jem.144.6.1657

Cited by 21 publications

(4 citation statements)

References 18 publications

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“…Our findings of poor outcomes in young men was consistent with reports from other cohorts in South Africa and eastern Africa [22][23][24]. In addition, a 2017 report showed that men aged 15-24 years had the lowest proportion of VS (41.5%) [20].…”

Section: Discussionsupporting

confidence: 91%

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Comparing effectiveness of first‐line antiretroviral therapy between peri‐urban and rural clinics in KwaZulu‐Natal, South Africa

et al. 2022

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Objectives: Viral suppression (VS) is the hallmark of successful antiretroviral therapy (ART) programmes. We sought to compare clinic retention, virological outcomes, drug resistance and mortality between peri-urban and rural settings in South Africa after first-line ART. Methods:Beginning in July 2014, 1000 (500 peri-urban and 500 rural) ART-naïve patients with HIV were enrolled and managed according to local standard of care. Clinic retention, virological suppression, virological failure (VF), genotypic drug resistance and mortality were assessed. The definition of VS was a viral load ≤1000 copies/ml. Time to event analyses were stratified by site, median age and gender. Kaplan-Meier curves were calculated and graphed with log-rank modelling to compare curves. Results:Based on 2741 patient-years of follow-up, retention and mortality did not differ between sites. Among all 1000 participants, 47%, 84% and 91% had achieved VS by 6, 12 and 24 months, respectively, which was observed earlier in the peri-urban site. At both sites, men aged < 32 years had the highest proportion of VF (15.5%), while women aged > 32 years had the lowest, at 7.1% (p = 0.018).Among 55 genotypes, 42 (76.4%) had at one or more resistance mutations, which F I G U R E 5 (a-c) Time to loss of virological response for participants in care overall (a), by site (b), and by age/gender (c). Log-rank p-values are provided if significant (< 0.05). The population analysed included only those participants who were suppressed at any point during the study. Therefore, the time interval extended from the date of first suppression until the end of the study, with date of first failure event as the event date. Censoring occurred for those who were lost to follow-up or died

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Section: Discussionsupporting

confidence: 91%

“…Given the migratory nature of the male population, being LTFU and changes in service provider are common. Additionally, inconsistent care for this population has had a documented effect of VF and death [23][24][25].…”

Section: Discussionmentioning

confidence: 99%

Comparing effectiveness of first‐line antiretroviral therapy between peri‐urban and rural clinics in KwaZulu‐Natal, South Africa

et al. 2022

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“…Work is now in progress to define whether the induction of the active component is related to the functions of microtubules or microfilaments. Very recently, ligand-specific esterase activation was observed by Henson et al (29) in the secretion process of platelet. If this situation could be applied to lymphocytes, the specific esterase might be activated by anti-Ig and it might be responsible for the activation of the cytoplasmic factor.…”

Section: Discussionmentioning

confidence: 93%

Induction and properties of cytoplasmic factor(s) which enhance nuclear nonhistone protein phosphorylation in lymphocytes stimulated by anti-Ig.

Nishizawa¹,

Kishimoto²,

Kikutani³

et al. 1977

The Journal of Experimental Medicine

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The receipt and translation of the signals responsible for the activation of B cells to immunoglobulin (Ig)-producing cells is largely a cell surface phenomenon and the specificity of B-cell response resides in cell surface-associated Ig molecules [see references (1) and (2)]. However, in many experiments the signals given through Ig receptors by anti-lg antibodies have not been stimulative but often served as negative signals for differentiation of B cells to plasma cells unless they were accompanied or followed by some T-cell activities (3-6). A series of our previous experiments (7-9), in which a sequential stimulation of rabbit lymphocytes with anti-lg antibody (anti-lg) and T-cell-derived soluble products (SF) I induced IgG production, have suggested that the signals given through Ig receptors were essential for the activation of B cells.Receptor-ligand interaction on the surface of lymphocytes induces several morphological and biochemical changes in lymphocytes, such as capping (10), movement (11), increased transport of amino acids (12), changes of Ca ++ influx (13), and increase or decrease of intracellular level of cyclic nucleotides (14, 15). However, the molecular mechanism with which the signals given through Ig receptors are transduced across membranes so as to induce proliferation and/or differentiation of B cells is entirely unknown. So far many experiments have been done to explore the mechanism of the transmission of membrane-mediated signals. For example, the experiments done by Edelman and his collaborators (16) showed that microtubules were intimately involved in the movement of cell surface-associated receptors. The important role of the esterase activation in the induction of movements of B cells with anti-lg was shown by Becker and Unanue (17). It should be noted, however, that the relation of the modulation of cell surface receptors or lymphocyte movements to B-cell activation is entirely unknown.Recently, it has been shown in several experiments that nonhistone nuclear proteins have an important role in regulating the gene expression of eukaryotic cells (18). In lymphocytes, Johnson et al. (19) showed an increase of the amounts and phosphorylations of nonhistone nuclear proteins by stimulation with mitogens. Johnson and Hadden (20) also showed that cyclic GMP induced an increased phosphorylation of nonhistone proteins as well as proliferation of lymphocytes, suggesting that the phosphorylation of nonhistone nuclear proteins may be involved in the activation process of lyrnphocytes.

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“…However, anaphylatoxin activity can be detected in vivo in several species (22,23) in spite of fluid-phase regulatory mechanisms. Besides these humoral factors, a regulatory phenomenon on the target cell level has been observed (3,24,25) : after incubation of cells with an anaphylatoxic stimulus, they do not respond a second time to the same or a related stimulus. Desensitization turned out to be stimulus specific.…”

mentioning

confidence: 99%

Low zone desensitization: a stimulus-specific control mechanism of cell response. Investigations on anaphylatoxin-induced platelet secretion.

Meuer¹,

Zanker²,

Hadding³

et al. 1982

The Journal of Experimental Medicine

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A variety of cells known to be involved in acute inflammatory reactions (mast cells and basophils, neutrophils, platelets, and macrophages) respond to the anaphylatoxic polypeptides C4a, C3a, or C5a with secretion of biogenic amines and secretion of various enzymes (1-11). These biological activities of anaphylatoxic complement fragments were studied mainly in vitro by use of purified or even synthetic substances (12-17).Calculations from experiments (18) performed in a recently developed guinea pig platelet system led to the conclusion that cleavage of <1% of the serum C3 or C5, leading to generation of C3a and C5a, could induce a marked release of platelet granule constituents. Sufficient amountsof anaphylatoxins may physiologically occur by the attack of various enzymes on C3 or C5 in the circulation or at a local site. Such high levels of activity require efficient control mechanisms.Investigations (19-21) with serum provided evidence for control mechanisms represented by humoral factors such as carboxypeptidases or proteases, which rapidly destroy the biologic activity of anaphylatoxins once they are generated from the native complement components. However, anaphylatoxin activity can be detected in vivo in several species (22, 23) in spite of fluid-phase regulatory mechanisms. Besides these humoral factors, a regulatory phenomenon on the target cell level has been observed (3, 24, 25) : after incubation of cells with an anaphylatoxic stimulus, they do not respond a second time to the same or a related stimulus. Desensitization turned out to be stimulus specific. In addition, desensitization could be achieved with low amounts of stimulating substances that were lower than those required to lead to a detectable release reaction (18).The experiments described in this study were performed to provide information on how cell reactivity to anaphylatoxic stimuli is influenced by the phenomenon of specific desensitization.We were especially interested in investigating how platelets respond to an anaphylatoxic stimulus generated in their presence, which seems more likely to happen under in vivo conditions than from exposure to preformed anaphylatoxic molecules.For these investigations, the platelet system was chosen because platelets can be * Supported by grants of the Deutsche Forschungsgemeinschaft:Sonderforschungsbereich 107 (Mainz). 698 J. Exp. MED.

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Activation of stimulus-specific serine esterases (proteases) in the initiation of platelet secretion. I. Demonstration with organophosphorus inhibitors.

Cited by 21 publications

References 18 publications

Comparing effectiveness of first‐line antiretroviral therapy between peri‐urban and rural clinics in KwaZulu‐Natal, South Africa

Comparing effectiveness of first‐line antiretroviral therapy between peri‐urban and rural clinics in KwaZulu‐Natal, South Africa

Induction and properties of cytoplasmic factor(s) which enhance nuclear nonhistone protein phosphorylation in lymphocytes stimulated by anti-Ig.

Low zone desensitization: a stimulus-specific control mechanism of cell response. Investigations on anaphylatoxin-induced platelet secretion.

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