Granulopoiesis inhibition in acute inflammation: comparative studies in healthy and leukaemic mice

It was demonstrated previously that mice undergoing an inflammatory reaction induced by subcutaneous (SC) implantation of copper rods, produce humoral factors that initially enhance, but subsequently inhibit, diffusion chamber (DC) granulopoiesis. This provided evidence that granulopoiesis is under the control of both humoral stimulators and inhibitors. In order to test the granulopoietic regulatory mechanism in leukaemic mice, we investigated the regulatory role of granulopoietic humoral inhibitors during in vivo granulopoiesis. We noticed that mice suffering from acute myeloid leukaemia (AML) are unable to augment the production of these humoral inhibitory factors when acute inflammation is induced, since no change in DC cell content was observed with or without prior inflammation. Moreover, unlike healthy mice, the serum of leukaemic mice withdrawn during the inhibition phase of acute inflammation did not show any inhibitory activity toward granulocyte—monocyte (GM) colony growth in vitro. Our results also show that increased levels of normal humoral inhibitors do not influence the proliferation and/or differentiation of leukaemic cells implanted in diffusion chamber cultures

Gender differences and inflammation: an in vitro model of blood cells stimulation in prepubescent children

Gender influences clinical presentations and markers in inflammatory diseases. In many chronic conditions, frequency of complications is greater in females, suggesting that continuous inflammatory reaction may induce greater damage in targeted organs and functions.Journal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe

The Number of X Chromosomes Influences Inflammatory Cytokine Production Following Toll-Like Receptor Stimulation

Sex differences are observed in the evolution of numerous inflammatory conditions. Women exhibit better clinical courses compared to men in acute inflammatory processes, yet worse prognosis in several chronic inflammatory diseases. Inflammatory markers are significantly different between prepubertal boys and girls, whose sex steroid levels are very low, suggesting genetics play a role. To evaluate the potential influence of the X chromosome, we studied cytokine production and protein phosphorylation following Toll-like receptor (TLR) activation in whole blood and purified neutrophils and monocytes of healthy adults of both sexes as well as subjects with Klinefelter syndrome. We recorded higher levels of inflammatory cytokines in men compared to both women and patients with Klinefelter syndrome following whole blood stimulation. In purified monocytes, production of inflammatory cytokines was also higher in men compared to women, while Klinefelter subjects expressed the same pattern of cytokine production as males, in contrast with whole blood analyses. These differences remained after adjusting for sex steroid levels. Our study revealed higher cytokine inflammatory responses in men than women, yet also compared to subjects with Klinefelter syndrome, who carry two copies of the X chromosome, like women, and thus potentially benefit from the cellular mosaicism of X-linked genes

Aspects de la physiopathologie de l'anémie et de la thrombocytopénie associées a une affection néoplasique chez l'enfant: rôles de l'erythropoïétine et de la thrombopoïétine.

Physiopathology of anaemia and thrombocytopaenia in children with malignancy: the role of erythropoietin and thrombopoietin. The aim of our work was to determine the role of an impaired erythropoietin (EPO) and thrombopoietin (TPO) production in development of, respectively, the anaemia and thrombocytopaenia in children with malignancy. Simultaneous dosage of EPO and of serum transferrin receptor have shown that anaemia in these patients is of central origin but related to a blunted EPO production. The same observation has been made in children at diagnosis either with acute leukaemia or solid tumour as well as during chemotherapy. In patients under maintenance chemotherapy for acute leukaemia, using long-term bone marrow cultures, we could detect an impaired supportive capacity of bone marrow micro-environment for erythropoiesis. The last part of this work has shown that thrombocytopaenia associated with acute leukaemia in children is accompanied by very high TPO levels as observed in other thrombocytopaenia of central origin, excepted in patients with acute leukaemia of myeloid origin. In these patients, TPO levels are inappropriately low in most cases. The low TPO levels are related to the presence of TPO receptor-expressing myeloid leukaemic cells, suggesting that TPO is "consumed" by blast cells expressing a functional TPO receptor.English AbstractJournal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe

La régulation de l'érythropoïèse: acquisitions récentes et incertitudes actuelles.

Rapid progress has occurred recently in characterizing the molecular structure of the glycoproteins controlling the growth, maturation and functional activities of hematopoietic cells. Several of these factors have been purified and cDNAs have been cloned, providing them in sufficient quantities for study and eventual clinical use. Both availability of these molecules and in vitro colony assays have revealed a large number of effects on erythroid differentiation. But, except erythropoietin (EPO), the physiological role of these hormones and their relative contributions to normal erythropoiesis remain to be specified. This paper attempts to review the most important data on this topic in 1990.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Contribution à l'étude de la physiopathologie de l'anémie et de la thrombocytopénie associées à une affection néoplasique chez l'enfant

L’objectif de notre travail était de déterminer le rôle joué par l’érythropoïétine et lathrombopoïétine, respectivement, dans l’anémie et la thrombocytopénie observéeschez des enfants souffrant d’une hémopathie maligne.Par le dosage simultané de la forme soluble du récepteur de la transferrine et del’érythropoïétine dans le sérum nous avons montré que l’anémie observée chez cespatients est bien la conséquence d’une réduction du nombre de progéniteursérythropoïétiques (atteinte médullaire centrale) mais que celle-ci n’est pas laconséquence d’une production insuffisante d’érythropoïétine. Nous avons fait lamême observation chez des enfants souffrant d’une tumeur solide nonhématologique et chez des patients en cours de traitement par chimiothérapie.Chez ces derniers patients, en appliquant un modèle de culture de moelle à longterme, nous avons pu démontrer l’existence d’une altération du microenvironnementmédullaire, probablement induite par la chimiothérapie, setraduisant par une réduction de son aptitude à supporter le développement de lalignée érythroïde. Ceci expliquant au moins partiellement l’inadéquation de laréponse érythropoïétique observée chez ces patients en réponse à l’anémie.Dans la dernière partie du travail, nous avons montré que la thrombocytopénie trèsfréquemment observée chez les patients leucémiques s’accompagne dans lamajorité des cas d’une élévation exponentielle de la concentration dethrombopoïétine, excepté dans les cas de leucémies de la lignée myéloïde. Chez cesderniers la concentration de thrombopoïétine est proche des valeurs observées chezdes sujets normaux alors qu’elle devrait être 10 à 100 fois plus élevée compte tenudu nombre de plaquettes extrêmement bas. Nous avons pu montrer que ces tauxtrès bas sont la conséquence de la liaison de la thrombopoïétine à un récepteurspécifique et fonctionnel présent à la surface des cellules leucémiques myéloïdesqui, en l’utilisant comme facteur de croissance, (stimulant leur prolifération etretardant leur mort cellulaire) « consomment » la thrombopoïétine présente dans lesérum.Doctorat en Sciences médicalesinfo:eu-repo/semantics/nonPublishe