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

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

Clinical Biochemistry, Ben-Gurion University of the Negev, Beer-Sheva 84105

Corresponding Author: ral{at}bgu.ac.il

It has been established that chronic inflammation of adipose tissue in obesity is characterized by secretion of proinflammatory cytokines and macrophage infiltration, but the initiating event(s) of the inflammatory cascade is still unknown. Since in classical immune responses neutrophils are the first to appear to the inflamed site prior to monocyte/macrophage infiltration, we hypothesized that neutrophil infiltration into adipose tissue may precede macrophage infiltration. 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, but not subcutaneous, 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 to 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 KC, respectively, compared with 24.8+1.5% in unstimulated neutrophils. The activation-dependent adherence required Ca2+ and could be mimicked by Mn2+, suggesting the involvement of integrins. The degree of surface exposure of CD11b (Mac-1) corresponded to the percentage of adhered neutrophils. The adherence was prevented by pre-incubating 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 co-immunoprecipitation of ICAM-1, indicating that the interaction is mediated by neutrophil CD11b and adipocyte ICAM-1.

Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

A. Kennedy, K. Martinez, C.-C. Chuang, K. LaPoint, and M. McIntosh
Saturated Fatty Acid-Mediated Inflammation and Insulin Resistance in Adipose Tissue: Mechanisms of Action and Implications
J. Nutr., January 1, 2009; 139(1): 1 - 4.
[Abstract] [Full Text] [PDF]