Elgazar-Carmon Vered, Rudich Assaf, Hadad Nurit, Levy Rachel
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.
J Lipid Res. 2008 Sep;49(9):1894-903. doi: 10.1194/jlr.M800132-JLR200. Epub 2008 May 23.
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.
肥胖状态下脂肪组织的慢性炎症如今已是一种既定现象，但炎症级联反应的起始事件仍不明晰。我们推测，如同在经典免疫反应中一样，中性粒细胞浸润脂肪组织可能先于巨噬细胞浸润。在此我们证明，在开始对C57BL/6J小鼠进行高脂喂养后的早期（3天和7天），中性粒细胞会短暂浸润腹腔内脂肪组织的实质。与第0天相比，在第3天和第7天，附睾周围脂肪中髓过氧化物酶的平均表达（代表中性粒细胞）显著增加了3.5倍（P < 0.01）和2.9倍（P < 0.03）。免疫组织化学分析显示中性粒细胞与脂肪细胞之间存在物理结合，体外黏附试验也证实了这一点：小鼠腹腔中性粒细胞以依赖其激活状态的方式黏附于3T3-L1小鼠脂肪细胞单层，分别通过佛波酯（PMA）或白细胞介素-8类似物CXCL1（KC）刺激后，黏附率分别为41.9 +/- 3.7%或29.5 +/- 2%，而未刺激的中性粒细胞黏附率分别为24.8 +/- 1.5%。CD11b（Mac-1）的表面暴露程度与黏附的中性粒细胞百分比相对应。用抗CD11b或抗ICAM-1抗体对中性粒细胞或脂肪细胞进行预孵育可阻止黏附。此外，从混合的中性粒细胞 - 脂肪细胞群体裂解物中对CD11b进行免疫沉淀导致ICAM-1的共免疫沉淀，表明这种相互作用是由中性粒细胞CD11b和脂肪细胞ICAM-1介导的。
