Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functionsof macrophages

We investigated the functions of adiponectin, an adipocyte-specific secreto ry 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, an d CFU-granulocyte, whereas it had no effect on that of burst-forming units- erythroid or mixed erythroid-myeloid CFU, In addition, adiponectin inhibite d proliferation of 4 of 9 myeloid cell lines but did not suppress prolifera tion of erythroid or lymphoid cell lines except for one cell line. These re sults suggest that adiponectin predominantly inhibits proliferation of myel omonocytic lineage cells. At least one mechanism of the growth inhibition i s induction of apoptosis because treatment of acute myelomonocytic leukemia lines with adiponectin induced the appearance of subdiploid peaks and olig onucleosomal DNA fragmentation. Aside from inhibiting growth of myelomonocy tic progenitors, adiponectin suppressed mature macrophage functions. Treatm ent of cultured macrophages with adiponectin significantly inhibited their phagocytic activity and their lipopolysaccharide-induced production of tumo r necrosis factor cu, Suppression of phagocytosis by adiponectin is mediate d 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 regula tor in hematopoiesis and immune systems and raise the possibility that it m ay be involved in ending inflammatory responses through its inhibitory func tions. (C) 2000 by The American Society of Hematology.