Neutrophils transiently infiltrate intra-abdominal fat early in the course of high-fat feeding

Vered Elgazar-Carmon, Assaf Rudich, Nurit Hadad, Rachel Levy

Research output: Contribution to journalArticlepeer-review

366 Scopus citations

Abstract

Chronic inflammation of adipose tissue in obesity is by now an established phenomenon, but the initiating event(s) of the inflammatory cascade are still unknown. We hypothesized that neutrophil infiltration into adipose tissue may precede macrophage infiltration as in classical immune responses. Here we demonstrate that early (3 and 7 days) after initiating high-fat feeding of C57BL/6J mice, neutrophils transiently infiltrate the parenchyma of intra-abdominal adipose tissue. Mean periepdidymal fat myeloperoxidase expression (representing neutrophils) was significantly increased 3.5-fold (P < 0.01) and 2.9-fold (P < 0.03), at days 3 and 7 compared with day 0. Immunohystochemistry analysis demonstrated a physical binding between neutrophils and adipocytes, which was supported by in vitro adherence assay: mouse peritoneal neutrophils adhered to a monolayer of 3T3-L1 mouse adipocytes, in a manner dependent on their activation state, 41.9 ± 3.7% or 29.5 ± 2%, by PMA or the IL-8 analog CXCL1 (KC), respectively, compared with 24.8 ± 1.5% in unstimulated neutrophils, respectively. The degree of surface exposure of CD11b (Mac-1) corresponded to the percentage of adhered neutrophils. The adherence was prevented by preincubating neutrophils or adipocytes with anti-CD11b or anti-ICAM-1 antibodies. Furthermore, immunoprecipitation of CD11b from lysates of a mixed neutrophil-adipocyte cell population resulted in coimmunoprecipitation of ICAM-1, indicating that the interaction is mediated by neutrophil CD11b and adipocyte ICAM-1.

Original languageEnglish
Pages (from-to)1894-1903
Number of pages10
JournalJournal of Lipid Research
Volume49
Issue number9
DOIs
StatePublished - 1 Sep 2008

Keywords

  • Adipocytes
  • Inflammation
  • Obesity

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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