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 α. 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.

Adiponectin prevents progression of steatohepatitis in mice by regulating oxidative stress and Kupffer cell phenotype polarization

“…18 We reported previously that adiponectin suppresses macrophage function. 39 In addition, adiponectin suppresses TNF-a, and stimulates IL-10 production in macrophages. 26,40 We reported pre- viously that lack of adiponectin increased serum TNF-a in the CDAA diet-fed mice.…”

Adiponectin and adiponectin receptor in relation to colorectal cancer progression

“…Several studies have shown that adiponectin induces apoptosis in breast cancer and myelomonocytic leukemia cell lines; this was mediated by downregulation of antiapoptotic genes such as Bcl-2 and Bcl-xL and upregulation of proapoptotic genes such as Bax and p53. 24,39,40 The reason for different apoptotic response between cancer cells is not clear, which necessitate further studies.…”

Adiponectin association with T‐cadherin protects against neointima proliferation and atherosclerosis

“…Increasing clinical evidence also links hypoadiponectinemia to the development of metabolic syndrome and atherosclerosis (8)(9)(10)(11)(12). Gain-or loss-of-function experiments in mice have suggested that adiponectin is a multifunctional protein that displays antiatherosclerotic (13)(14)(15), antidiabetic (16)(17)(18), anti-inflammatory (19), and antifibrotic properties (20,21), among others.…”