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Neutrophils Sequestered in the Liver Moderate Proinflammatory Cytokine/Chemokine Production by Kupffer Cells
Author(s) -
Holub Martin,
Wintermeyer Philip,
Gregory Stephen H.
Publication year - 2008
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/fasebj.22.1_supplement.1065.19
Subject(s) - chemokine , kupffer cell , cytokine , proinflammatory cytokine , liver injury , interleukin 8 , biology , immunology , inflammation , microbiology and biotechnology , endocrinology
The liver plays a major role in clearing bacteria from the bloodstream. Clearance is often attributed to Kupffer cells, which line the hepatic sinusoids and comprise ≈35% of the nonparenchymal liver cell population in mice. Rather, we reported previously that most bacteria taken up by the liver are killed by immigrating neutrophils. Ingestion by Kupffer cells and timely elimination of these neutrophils suppresses inflammation and tissue injury that might otherwise ensue. To determine the effect of ingested neutrophils on cytokine production by Kupffer cells, mice were treated with anti‐neutrophil monoclonal antibody. Kupffer cells isolated from antibody‐treated control (non‐infected) mice, as well as from ‐treated mice at 2 hours postinfection with Listeria , exhibited a marked increase in intracellular myeloperoxidase activity demonstrating the role of Kupffer cells in eliminating dead neutrophils. Neutrophil ingestion exerted a significant effect on cytokine/chemokine mRNA expression and protein production by Kupffer cells subsequent to Listeria infection. IL‐6, IL‐12, IL‐10, KC and MIP‐1α production by neutrophil‐containing Kupffer cells was sharply diminished. These findings demonstrate the role of neutrophils in regulating cytokine/chemokine production by Kupffer cells and, thus, moderating the proinflammatory response to bacteria taken up by the liver. Supported by NIH Grant DK068097.