title: Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages.
abstract: We investigated the functions of adiponectin, an adipocyte-specific secretory protein and a new member of the family of soluble defense collagens, in hematopoiesis and immune responses. Adiponectin suppressed colony formation from colony-forming units (CFU)-granulocyte-macrophage, CFU-macrophage, and CFU-granulocyte, whereas it had no effect on that of burst-forming units-erythroid or mixed erythroid-myeloid CFU. In addition, adiponectin inhibited proliferation of 4 of 9 myeloid cell lines but did not suppress proliferation of erythroid or lymphoid cell lines except for one cell line. These results suggest that adiponectin predominantly inhibits proliferation of myelomonocytic lineage cells. At least one mechanism of the growth inhibition is induction of apoptosis because treatment of acute myelomonocytic leukemia lines with adiponectin induced the appearance of subdiploid peaks and oligonucleosomal DNA fragmentation. Aside from inhibiting growth of myelomonocytic progenitors, adiponectin suppressed mature macrophage functions. Treatment of cultured macrophages with adiponectin significantly inhibited their phagocytic activity and their lipopolysaccharide-induced production of tumor necrosis factor alpha. Suppression of phagocytosis by adiponectin is mediated by one of the complement C1q receptors, C1qRp, because this function was completely abrogated by the addition of an anti-C1qRp monoclonal antibody. These observations suggest that adiponectin is an important negative regulator in hematopoiesis and immune systems and raise the possibility that it may be involved in ending inflammatory responses through its inhibitory functions. (Blood. 2000;96:1723-1732)
authors.affiliation: Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan. yokota@imed2.med.osaka-u.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Yokota
authors.forename: K
authors.initials: K
authors.lastname: Oritani
authors.forename: I
authors.initials: I
authors.lastname: Takahashi
authors.forename: J
authors.initials: J
authors.lastname: Ishikawa
authors.forename: A
authors.initials: A
authors.lastname: Matsuyama
authors.forename: N
authors.initials: N
authors.lastname: Ouchi
authors.forename: S
authors.initials: S
authors.lastname: Kihara
authors.forename: T
authors.initials: T
authors.lastname: Funahashi
authors.forename: A J
authors.initials: AJ
authors.lastname: Tenner
authors.forename: Y
authors.initials: Y
authors.lastname: Tomiyama
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuzawa
mesh_terms: D052242:Adiponectin; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002352:Carrier Proteins; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D003094:Collagen / Q000494:pharmacology*; D003114:Colony-Forming Units Assay; D005786:Gene Expression Regulation / Q000187:drug effects; D018922:HL-60 Cells; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D018960:Hyaluronan Receptors; D036341:Intercellular Signaling Peptides and Proteins; D019169:Jurkat Cells; D020014:K562 Cells; D015479:Leukemia, Myelomonocytic, Acute / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008562:Membrane Glycoproteins; D051379:Mice; D024101:Mitochondrial Proteins; D010587:Phagocytosis / Q000187:drug effects; D011506:Proteins / Q000378:metabolism / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D011951:Receptors, Complement / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D020298:U937 Cells
chemical_list: D052242:Adiponectin; C087299:C1QBP protein, human; C490193:C1qbp protein, mouse; D002352:Carrier Proteins; D018960:Hyaluronan Receptors; D036341:Intercellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011951:Receptors, Complement; D014409:Tumor Necrosis Factor-alpha; C032402:complement 1q receptor; D003094:Collagen