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Elevated soluble ICAM‐1 levels induce immune deficiency and increase adiposity in mice
Author(s) -
Wang HongWei,
Babic Aleksandar M.,
Mitchell Heather A.,
Liu Kui,
Wagner Denisa D.
Publication year - 2005
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.04-3094fje
Subject(s) - immune system , genetically modified mouse , peritoneal cavity , icam 1 , endocrinology , medicine , biology , extracellular , transgene , ratón , inflammation , intracellular , chemistry , immunology , cell adhesion molecule , microbiology and biotechnology , biochemistry , anatomy , gene
ABSTRACT Elevated soluble intercellular adhesion molecule‐1 (sICAM‐1) levels have been found in many pathological conditions, including obesity. To determine the effects of elevated sICAM‐1 on immune responses and metabolism, we generated a transgenic mouse model overexpressing the extracellular domain of mouse ICAM‐1 in the liver. The mice, showing 10‐fold higher sICAM‐1 levels than wild‐type mice, presented elevated neutrophil count. Despite this, after intraperitoneal injection of thioglycollate, neutrophil recruitment into the peritoneal cavity was reduced, and the delayed macrophage recruitment was also affected in the transgenic mice compared with wild‐type mice. Inhibition of contact hypersensitivity response in the sICAM‐1 transgenic mice was comparable to ICAM‐1‐deficient mice and characterized by significantly less ear swelling and inflammatory cell infiltration than in wild‐type mice. sICAM‐1transgenic mice were more susceptible to weight gain on a Western‐type diet than wild‐type mice, and older animals showed excessive fat accumulation, again reminiscent of ICAM‐1‐deficient mice. Together, these data indicate that sICAM‐1 interferes with ICAM‐1‐mediated cell‐cell interactions, which could produce immune‐suppressant effects and alteration of metabolism in persons with high levels of this soluble adhesion receptor.