Neutrophils transiently infiltrate intra-abdominal fat early in the course of high-fat feeding.
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. Immunohistochemistry 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.
Elgazar-Carmon
Vered
V
Infectious Diseases Laboratory, The S. Daniel Abraham Center for Health and Nutrition, Faculty of Health Sciences, Soroka Medical Center and Ben-Gurion University of the Negev, Beer Sheva, Israel.
Rudich
Assaf
A
Hadad
Nurit
N
Levy
Rachel
R
D041721:3T3-L1 Cells; D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D039481:CD11b Antigen / Q000502:physiology; D002448:Cell Adhesion; D004041:Dietary Fats / Q000008:administration & dosage*; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D008297:Male; D051379:Mice; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000276:immunology*
D039481:CD11b Antigen; D004041:Dietary Fats; D018799:Intercellular Adhesion Molecule-1