Yoshihiko Tani

Activation of JAK-STAT and MAP Kinases by Leukemia Inhibitory Factor Through gp130 in Cardiac Myocytes

BACKGROUND Interleukin (IL)-6-related cytokines share gp130 as the signal-transducing protein. Downstream of gp130, two signal-transducing pathways have been recognized, the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway and the Ras-mitogen-activated protein kinase (MAPK) pathway. To determine whether these two signaling pathways through gp130 are present in cardiac myocytes, we examined their activation by using leukemia inhibitory factor (LIF), which is a member of the IL-6 cytokine family. METHODS AND RESULTS Lysates from neonatal rat cardiac myocytes were immunoprecipitated with anti-gp130, anti-JAK1, or anti-STAT3 antibody and blotted with anti-phosphotyrosine antibody. Tyrosine phosphorylation of gp130, JAK1, and STAT3 was observed after LIF stimulation in cardiac myocytes. MAPKs were maximally activated 5 minutes after LIF stimulation. Furthermore, anti-gp130 antibody significantly inhibited the LIF-induced activation of JAK1, STAT3, and MAPKs. To examine whether these signaling pathways were also activated in the adult heart in vivo, LIF was injected intravenously into a 6-week-old mouse, and the heart was examined subsequently. gp130, STAT3, and MAPKs were activated in the heart after LIF treatment. CONCLUSIONS These results demonstrate for the first time that a JAK-STAT pathway and a MAPK pathway are present down-stream of gp130 in cardiac myocytes and are rapidly activated by LIF both in vitro and in vivo. Activation of gp130 constitutes a novel signaling pathway in cardiac myocytes.

Blood group terminology 2004: from the International Society of Blood Transfusion committee on terminology for red cell surface antigens

1 Bristol Institute for Transfusion Sciences, Bristol, UK 2 Growing your Knowledge, Spit Junction, NSW, Australia 3 American Red Cross Blood Services, Los Angeles-Orange Counties Region, Los Angeles, CA, USA 4 Biotechnology Research Centre, Auckland University of Technology, Auckland, New Zealand 5 Regional Blood Transfusion Center, Department of Clinical Immunology, University Hospital, Arhus N, Denmark 6 Department of Pathology, University Hospitals UH-2G332, Ann Arbor, Michigan, USA 7 Reference Laboratory for Immunohematology and Blood Groups, National Blood Services Centre, Tel Hashomer, Israel 8 New York Blood Center, New York, NY, USA 9 Ortho-Clinical Diagnostics, Raritan, NJ, USA 10 Drexel University College of Medicine, Philadelphia, PA, USA 11 Gamma Biologicals Inc (subsidiary of Immunocor Inc), Houston, TX, USA 12 Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam, the Netherlands 13 Centre national de Reference pour les Groupes sanguines (CNTS), Paris, France 14 International Blood Group Reference Laboratory, Bristol, UK 15 Finnish Red Cross Blood Transfusion Service, Helsinki, Finland 16 South African National Blood Service, East Coast Region, Pinetown, South Africa 17 Osaka Red Cross Blood Center, Osaka, Japan 18 Blood Bank, Hospital Sirio-Libanes, Sao Paulo, Brazil 19 Rh Laboratory, University of Manitoba, Winnipeg, Manitoba, Canada

International Society of Blood Transfusion Working Party on red cell immunogenetics and blood group terminology: Berlin report.

The International Society of Blood Transfusion Working Party on red cell immunogenetics and blood group terminology convened during the International congress in Cancun, July 2012. This report details the newly identified antigens in existing blood group systems and presents three new blood group systems.

ABCB6 is dispensable for erythropoiesis and specifies the new blood group system Langereis.

The human ATP-binding cassette (ABC) transporter ABCB6 has been described as a mitochondrial porphyrin transporter essential for heme biosynthesis, but it is also suspected to contribute to anticancer drug resistance, as do other ABC transporters located at the plasma membrane. We identified ABCB6 as the genetic basis of the Lan blood group antigen expressed on red blood cells but also at the plasma membrane of hepatocellular carcinoma (HCC) cells, and we established that ABCB6 encodes a new blood group system (Langereis, Lan). Targeted sequencing of ABCB6 in 12 unrelated individuals of the Lan(−) blood type identified 10 different ABCB6 null mutations. This is the first report of deficient alleles of this human ABC transporter gene. Of note, Lan(−) (ABCB6−/−) individuals do not suffer any clinical consequences, although their deficiency in ABCB6 may place them at risk when determining drug dosage.

International Society of Blood Transfusion Committee on Terminology for Red Cell Surface Antigens: Cape Town report.

The Committee met in Cape Town during the 2006 Inter-national Society of Blood Transfusion (ISBT) Congress (seeAppendix 1 for Committee members). Some changes to theclassification documented in Blood Group Terminology 2004[1] were agreed and are described below. The full updatedclassification can be found on the Blood Group Terminologywebsite at http://www.blood.co.uk/ibgrl. New antigens wereadded to the MNS, Kell, Scianna, Cromer, Indian, Knops,and JMH systems (Table 1). In line with convention, aminoacid positions are numbered with the translation-initiatingmethionine as 1, although the more traditional numberingfor glycophorin A, with number 1 representing the first aminoacid of the mature protein, is also provided.

In Vitro Proliferation Potential of AC133 Positive Cells in Peripheral Blood

AC133 antigen is a novel marker for human hematopoietic stem/progenitor cells. In this study, we examined the expression and proliferation potential of AC133+ cells obtained from steady‐state peripheral blood (PB). The proportion of AC133+ cells in the CD34+ subpopulation of steady‐state PB was significantly lower than that of cord blood (CB), although that of cytokine‐mobilized PB was higher than that of CB. The proliferation potential of AC133+CD34+ and AC133−CD34+ cells was examined by colony‐forming analysis and analysis of long‐term culture‐initiating cells (LTC‐IC). Although the total number of colony‐forming cells was essentially the same in the AC133+CD34+ fraction as in the AC133−CD34+ fraction, the proportion of LTC‐IC was much higher in the AC133+CD34+ fraction. Virtually no LTC‐IC were detected in the AC133−CD34+ fraction. In addition, the features of the colonies grown from these two fractions were quite different. Approximately 70% of the colonies derived from the AC133+CD34+ fraction were granulocyte‐macrophage colonies, whereas more than 90% of the colonies derived from the AC133−CD34+ fraction were erythroid colonies. Furthermore, an ex vivo expansion study observed expansion of colony‐forming cells only in the AC133+CD34+ population, and not in the AC133−CD34+ population. These findings suggest that to isolate primitive hematopoietic cells from steady‐state PB, selection by AC133 expression is better than selection by CD34 expression.

International Society of Blood Transfusion Committee on terminology for red blood cell surface antigens: Macao report

The committee met in Macao Special Administrative Region,China, during the 2008 International Society of Blood Trans-fusion (ISBT) Congress. Some changes to the classificationdocumented in Blood Group Terminology 2004 [1] and updatedin 2007 [2] were agreed and are described below. The fullupdated classification can be found on the blood groupterminology website at http://www.blood.co.uk/ibgrl. A newblood group system, the RHAG system, was established andnew antigens were added to the Rh, Kell, and Dombrocksystems (Table 1). A total of 308 antigens are now recognized,270 of which are clustered in 30 blood group systems.

International Society of Blood Transfusion Working Party on red cell immunogenetics and blood group terminology: Berlin report: Red cell immunogenetics and blood group terminology

J. R. Storry, L. Castilho, G. Daniels, W. A. Flegel, G. Garratty, C. L. Francis, J. M. Moulds, J. J. Moulds, M. L. Olsson, J. Poole, M. E. Reid, P. Rouger, E. van der Schoot, M. Scott, E. Smart, Y. Tani, L.-C. Yu, S. Wendel, C. Westhoff, V. Yahalom & T. Zelinski Clinical Immunology and Transfusion Medicine, University and Regional Laboratories, Lund, Sweden University of Campinas ⁄ Hemocentro, Campinas, Brazil Bristol Institute for Transfusion Sciences and IBGRL, NHSBT, Bristol, UK NIH Clinical Center, Department of Transfusion Medicine, Bethesda, MD, USA American Red Cross Blood Services, Pomona, CA, USA New York Blood Center, New York, NY, USA LifeShare Blood Centers, Shreveport, LA, USA Department of Laboratory Medicine, Division of Haematology and Transfusion Medicine, Lund University, Lund, Sweden Centre National de Référence pour les Groupes sanguines, Paris, France Sanquin Research at CLB, Amsterdam, The Netherlands Durban, South Africa Osaka Red Cross Blood Center, Osaka, Japan Mackay Memorial Hospital and National Taiwan University, Taipei, Taiwan Blood Bank, Hospital Sirio-Libanes, São Paulo, Brazil NBGRL Magen David Adom, Ramat Gan, Israel Rh Laboratory, Winnipeg, MB, Canada

A forward genetic screen identifies erythrocyte CD55 as essential for Plasmodium falciparum invasion

A way to dissect malarias secrets Malaria has exerted a strong selective force on the human genome. However, efforts to identify host susceptibility factors have been hindered by the absence of a nucleus in red blood cells. Egan et al. developed an approach involving blood stem cells to discover host factors critical for Plasmodium falciparum infection of red blood cells. The authors identified an essential host receptor for parasite invasion that could provide a target for malaria therapeutics. Science, this issue p. 711 A screening approach reveals host factors critical for human malaria parasite invasion of red blood cells. Efforts to identify host determinants for malaria have been hindered by the absence of a nucleus in erythrocytes, which precludes genetic manipulation in the cell in which the parasite replicates. We used cultured red blood cells derived from hematopoietic stem cells to carry out a forward genetic screen for Plasmodium falciparum host determinants. We found that CD55 is an essential host factor for P. falciparum invasion. CD55-null erythrocytes were refractory to invasion by all isolates of P. falciparum because parasites failed to attach properly to the erythrocyte surface. Thus, CD55 is an attractive target for the development of malaria therapeutics. Hematopoietic stem cell–based forward genetic screens may be valuable for the identification of additional host determinants of malaria pathogenesis.

Terminology for red cell surface antigens

The Working Party met at Makuhari Messe, Japan on 31 March 1996. A few changes to the current classification, documented in Blood Group Terminology 1995 [1], were agreed and these are described below.