Limits...
Microparticles release by adipocytes act as "find-me" signals to promote macrophage migration.

Eguchi A, Mulya A, Lazic M, Radhakrishnan D, Berk MP, Povero D, Gornicka A, Feldstein AE - PLoS ONE (2015)

Bottom Line: The release of MPs was highly regulated and dependent on caspase 3 and Rho-associated kinase.Further analysis identified these MPs as a central chemoattractant in vitro and in vivo.In addition, intravenously transplanting circulating MPs from the ob/ob mice lead to activation of monocytes in circulation and adipose tissue of the wild type mice.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, University of California San Diego (UCSD), La Jolla, California, United States of America.

ABSTRACT
Macrophage infiltration of adipose tissue during weight gain is a central event leading to the metabolic complications of obesity. However, what are the mechanisms attracting professional phagocytes to obese adipose tissue remains poorly understood. Here, we demonstrate that adipocyte-derived microparticles (MPs) are critical "find-me" signals for recruitment of monocytes and macrophages. Supernatants from stressed adipocytes stimulated the attraction of monocyte cells and primary macrophages. The activation of caspase 3 was required for release of these signals. Adipocytes exposed to saturated fatty acids showed marked release of MPs into the supernatant while common genetic mouse models of obesity demonstrate high levels of circulating adipocyte-derived MPs. The release of MPs was highly regulated and dependent on caspase 3 and Rho-associated kinase. Further analysis identified these MPs as a central chemoattractant in vitro and in vivo. In addition, intravenously transplanting circulating MPs from the ob/ob mice lead to activation of monocytes in circulation and adipose tissue of the wild type mice. These data identify adipocyte-derived MPs as novel "find me" signals that contributes to macrophage infiltration associated with obesity.

No MeSH data available.


Related in: MedlinePlus

Adipocyte-derived MPs mediates attraction of macrophages in vitro and in vivo.(A) In vitro chemotaxis assay of MPs-free supernatant and MPs from adipocytes treated with palmitic acid. Values represent mean ± S.D. ***P < 0.001 compared to controls. (B-F) C57BL/6 mice were injected intraperitoneally with 1x106 adipocyte-derived MPs (isolated from 3T3-L1 adipocytes treated with 0.5 mM palmitic acid or without palmitic acid) or controls (n = 3 each group). (B) Four days post injection infiltrated cells were isolated from peritoneal cavity by lavage and counted. (C-F) flow cytometry analysis of infiltrated cells. The infiltrated cells were stained by CD45 (leukocyte common antigen) (C), CD11b (monocytes) (D), F4/80 (macrophages) (E), or Ly6G (neutrophils) (F). Values represent mean ± S.E.M. (D) In vivo macrophages migration. C57BL/6 mice were injected intraperitoneally with 1x106 palmitic acid-derived MPs or vehicle alone (n = 5 per group). Three days post injection; macrophages were isolated from peritoneal cavity by lavage. Number of macrophages present in peritoneal cavity was counted. Values represent mean ± S.E.M.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4388837&req=5

pone.0123110.g004: Adipocyte-derived MPs mediates attraction of macrophages in vitro and in vivo.(A) In vitro chemotaxis assay of MPs-free supernatant and MPs from adipocytes treated with palmitic acid. Values represent mean ± S.D. ***P < 0.001 compared to controls. (B-F) C57BL/6 mice were injected intraperitoneally with 1x106 adipocyte-derived MPs (isolated from 3T3-L1 adipocytes treated with 0.5 mM palmitic acid or without palmitic acid) or controls (n = 3 each group). (B) Four days post injection infiltrated cells were isolated from peritoneal cavity by lavage and counted. (C-F) flow cytometry analysis of infiltrated cells. The infiltrated cells were stained by CD45 (leukocyte common antigen) (C), CD11b (monocytes) (D), F4/80 (macrophages) (E), or Ly6G (neutrophils) (F). Values represent mean ± S.E.M. (D) In vivo macrophages migration. C57BL/6 mice were injected intraperitoneally with 1x106 palmitic acid-derived MPs or vehicle alone (n = 5 per group). Three days post injection; macrophages were isolated from peritoneal cavity by lavage. Number of macrophages present in peritoneal cavity was counted. Values represent mean ± S.E.M.

Mentions: We next examined the effects on macrophages of purified adipocyte-derived MPs from control and stressed adipocytes and demonstrated that MPs formed by treatment of adipocytes with palmitic acid induce marked macrophage migration (Fig 4A). While supernatants of these cells depleted of MPs lost their chemotactic activity (Fig 4A). Next, to test whether adipocyte-derived MPs could induce macrophage migration in vivo C57BL/6 mice were injected intraperitoneally with cell-specific MPs from palmitic acid or control treated adipocytes. Injection of MPs derived from palmitic acid treated adipocytes resulted in an almost two-fold increase of infiltrated cells compared to control MPs or saline injection after four days post injection (Fig 4B). All infiltrated cells were leukocytes (CD45 LCA; white cell common antigen) (Fig 4C) and the main population of leukocytes was monocytes (CD11b positive) (Fig 4D) and macrophages (F4/80 positive) (Fig 4E), but not neutrophils (Ly6G negative) (Fig 4F).


Microparticles release by adipocytes act as "find-me" signals to promote macrophage migration.

Eguchi A, Mulya A, Lazic M, Radhakrishnan D, Berk MP, Povero D, Gornicka A, Feldstein AE - PLoS ONE (2015)

Adipocyte-derived MPs mediates attraction of macrophages in vitro and in vivo.(A) In vitro chemotaxis assay of MPs-free supernatant and MPs from adipocytes treated with palmitic acid. Values represent mean ± S.D. ***P < 0.001 compared to controls. (B-F) C57BL/6 mice were injected intraperitoneally with 1x106 adipocyte-derived MPs (isolated from 3T3-L1 adipocytes treated with 0.5 mM palmitic acid or without palmitic acid) or controls (n = 3 each group). (B) Four days post injection infiltrated cells were isolated from peritoneal cavity by lavage and counted. (C-F) flow cytometry analysis of infiltrated cells. The infiltrated cells were stained by CD45 (leukocyte common antigen) (C), CD11b (monocytes) (D), F4/80 (macrophages) (E), or Ly6G (neutrophils) (F). Values represent mean ± S.E.M. (D) In vivo macrophages migration. C57BL/6 mice were injected intraperitoneally with 1x106 palmitic acid-derived MPs or vehicle alone (n = 5 per group). Three days post injection; macrophages were isolated from peritoneal cavity by lavage. Number of macrophages present in peritoneal cavity was counted. Values represent mean ± S.E.M.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4388837&req=5

pone.0123110.g004: Adipocyte-derived MPs mediates attraction of macrophages in vitro and in vivo.(A) In vitro chemotaxis assay of MPs-free supernatant and MPs from adipocytes treated with palmitic acid. Values represent mean ± S.D. ***P < 0.001 compared to controls. (B-F) C57BL/6 mice were injected intraperitoneally with 1x106 adipocyte-derived MPs (isolated from 3T3-L1 adipocytes treated with 0.5 mM palmitic acid or without palmitic acid) or controls (n = 3 each group). (B) Four days post injection infiltrated cells were isolated from peritoneal cavity by lavage and counted. (C-F) flow cytometry analysis of infiltrated cells. The infiltrated cells were stained by CD45 (leukocyte common antigen) (C), CD11b (monocytes) (D), F4/80 (macrophages) (E), or Ly6G (neutrophils) (F). Values represent mean ± S.E.M. (D) In vivo macrophages migration. C57BL/6 mice were injected intraperitoneally with 1x106 palmitic acid-derived MPs or vehicle alone (n = 5 per group). Three days post injection; macrophages were isolated from peritoneal cavity by lavage. Number of macrophages present in peritoneal cavity was counted. Values represent mean ± S.E.M.
Mentions: We next examined the effects on macrophages of purified adipocyte-derived MPs from control and stressed adipocytes and demonstrated that MPs formed by treatment of adipocytes with palmitic acid induce marked macrophage migration (Fig 4A). While supernatants of these cells depleted of MPs lost their chemotactic activity (Fig 4A). Next, to test whether adipocyte-derived MPs could induce macrophage migration in vivo C57BL/6 mice were injected intraperitoneally with cell-specific MPs from palmitic acid or control treated adipocytes. Injection of MPs derived from palmitic acid treated adipocytes resulted in an almost two-fold increase of infiltrated cells compared to control MPs or saline injection after four days post injection (Fig 4B). All infiltrated cells were leukocytes (CD45 LCA; white cell common antigen) (Fig 4C) and the main population of leukocytes was monocytes (CD11b positive) (Fig 4D) and macrophages (F4/80 positive) (Fig 4E), but not neutrophils (Ly6G negative) (Fig 4F).

Bottom Line: The release of MPs was highly regulated and dependent on caspase 3 and Rho-associated kinase.Further analysis identified these MPs as a central chemoattractant in vitro and in vivo.In addition, intravenously transplanting circulating MPs from the ob/ob mice lead to activation of monocytes in circulation and adipose tissue of the wild type mice.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, University of California San Diego (UCSD), La Jolla, California, United States of America.

ABSTRACT
Macrophage infiltration of adipose tissue during weight gain is a central event leading to the metabolic complications of obesity. However, what are the mechanisms attracting professional phagocytes to obese adipose tissue remains poorly understood. Here, we demonstrate that adipocyte-derived microparticles (MPs) are critical "find-me" signals for recruitment of monocytes and macrophages. Supernatants from stressed adipocytes stimulated the attraction of monocyte cells and primary macrophages. The activation of caspase 3 was required for release of these signals. Adipocytes exposed to saturated fatty acids showed marked release of MPs into the supernatant while common genetic mouse models of obesity demonstrate high levels of circulating adipocyte-derived MPs. The release of MPs was highly regulated and dependent on caspase 3 and Rho-associated kinase. Further analysis identified these MPs as a central chemoattractant in vitro and in vivo. In addition, intravenously transplanting circulating MPs from the ob/ob mice lead to activation of monocytes in circulation and adipose tissue of the wild type mice. These data identify adipocyte-derived MPs as novel "find me" signals that contributes to macrophage infiltration associated with obesity.

No MeSH data available.


Related in: MedlinePlus