title: Designer cytokine hyper interleukin 11 (H11) is a megakaryopoietic factor.
abstract: Interleukin-11 (IL-11) displays megakaryopoietic activity. We constructed super-cytokine Hyper- IL11 (H11) by linking soluble IL-11 receptor α (sIL-11Rα) with IL-11, which directly targets β-receptor (gp130) signal transducing subunit. The effects of H11 on hematopoiesis with a focus on megakaryopoiesis were studied. The expansion, differentiation and type of colony formation of cord blood progenitor Lin-CD34+ cells were analyzed. H11 was more effective than recombinant human IL-11 (rhIL-11) in enhancement of the Lin-CD34+ cells expansion and differentiation into megakaryocytes (Mk). It induced higher expression of CD41a and CD61 antigens, resulting in a substantially larger population of CD34-CD41a(high)CD61(high) cells. H11 treatment led to increased number of small and mainly medium megakaryocyte colony formation (Mk-CFU). Moreover, it induced the formation of a small number of large colonies, which were not observed following rhIL-11 treatment. Significantly higher number of H11 derived Mk colonies released platelets-like particles (PLP). Furthermore, H11 was considerably more potent than rhIL-11 in promoting differentiation of Lin-CD43+ cells toward erythrocytes. Our results indicate that H11 is more effective than rhIL-11 in enhancing expansion of early progenitors and directing them to megakaryocyte and erythroid cells and in inducing maturation of Mk. Thus, H11 may prove beneficial for thrombocytopenia treatment and/or an ex vivo expansion of megakaryocytes.
authors.affiliation: Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Centre, Poznan, 61-866, Poland. hanna.dams-kozlowska@wco.pl
authors.forename: Hanna
authors.initials: H
authors.lastname: Dams-Kozlowska
authors.forename: Eliza
authors.initials: E
authors.lastname: Kwiatkowska-Borowczyk
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Gryska
authors.forename: Andrzej
authors.initials: A
authors.lastname: Mackiewicz
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology; D041905:Erythroid Cells / Q000166:cytology / Q000378:metabolism; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D017370:Interleukin-11 / Q000378:metabolism* / Q000494:pharmacology; D053703:Interleukin-11 Receptor alpha Subunit / Q000378:metabolism*; D015850:Interleukin-6 / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013921:Thrombocytopenia / Q000235:genetics / Q000378:metabolism; D034061:Thrombopoiesis / Q000235:genetics / Q000502:physiology
chemical_list: D018952:Antigens, CD34; D016207:Cytokines; C508428:IL11RA protein, human; D017370:Interleukin-11; D053703:Interleukin-11 Receptor alpha Subunit; D015850:Interleukin-6
keywords: hyper cytokine; interleukin 11; megakaryopoiesis; platelets; stem cells; thrombocytopenia.