An essential role of macrophage inflammatory protein 1α/CCL3 on the expression of host's innate immunities against infectious complications

Hitoshi Takahashi, Tsuguhiko Tashiro, Masaru Miyazaki, Makiko Kobayashi, Richard B Pollard, Fujio Suzuki

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Sepsis was induced by well-controlled cecal ligation and puncture (CLP) in macrophage inflammatory protein 1α (MIP-1α)/CCL3 knock-out (CCL3-/-) and severe combined immunodeficiency (SCID) mice. CCL3-/- mice and their littermates (CCL3+/+ mice) treated with anti-CCL3 monoclonal antibodies were susceptible (0-20% survival) to CLP-induced sepsis, and CCL3-/- mice supplemented with recombinant (r)CCL3 (250 ng/mouse) and CCL3+/+ mice were resistant (70-80% survival). The resistance of SCID mice to CLP was markedly improved by the rCCL3 administration (88% survival), and SCID mice treated with saline were shown to be middling resistant to the same CLP (45% survival). However, the resistance of SCID-M mice (SCID mice depleted of the macrophage function) to CLP was not improved by the rCCL3 administration (11% survival), and 41% of SCID-M mice reconstituted with normal peritoneal macrophages and 79% of SCID-M mice inoculated with CCL3-treated peritoneal macrophages survived. In addition, the resistance of SCID-MN mice (SCID mice depleted of functional macrophages and neutrophils) to CLP was improved by the inoculation of CCL3-treated macrophages (78% survival), and all of SCID-MN mice inoculated with CCL3-treated neutrophils died. CCL3 is shown to be essential to the host resistance against bacterial sepsis. Macrophages but not neutrophils are highlighted as the major effector cells when protective innate immunities against sepsis are improved by CCL3.

Original languageEnglish (US)
Pages (from-to)1190-1197
Number of pages8
JournalJournal of Leukocyte Biology
Volume72
Issue number6
StatePublished - Dec 1 2002

Keywords

  • CCL3 knockout mice
  • SCID mice
  • Sepsis

ASJC Scopus subject areas

  • Cell Biology

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