CSF-1 (M-CSF) differentially sensitizes mononuclear phagocyte subpopulations to endotoxin in vivo: A potential pathway that regulates the severity of gram-negative infections

Andrei I. Chapoval, Sonya J. Kamdar, Sergey G. Kremlev, Robert Evans

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

CSF-1 is known to prime mononuclear phagocytes (MNP) for inflammatory stimuli in vitro. We hypothesized that CSF-1 in vivo can sensitize the host to the increased production of endotoxic shock mediators such as tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6). Indeed, when CSF-1- primed mice were challenged with lipopolysaccharide (LPS), increased levels of serum IL-6 and TNF-α were detected. Both intravenous and intraperitoneal injections of CSF-1 resulted in increased sensitivity to LPS challenge, which induced maximum increases in serum IL-6 when administered via the intraperitoneal route. The peak serum IL-6 production in control and CSF-1- primed mice occurred 2-3 h after LPS injection, whereas that of TNF-α occurred by 1-2 h. When peripheral blood leukocytes, spleen cells, and resident peritoneal cells (PC) were isolated from CSF-1-primed mice injected with LPS, only the PC were shown to release IL-6 constitutively and none released TNF-α. A comparison of mRNA isolated from various cells and tissues after intraperitoneal CSF-1 priming indicated that only PC expressed IL-6 mRNA, whereas PC, liver, and spleen expressed TNF-α mRNA. All tissues showed increased levels of IL-6 and TNF-α mRNA in response to LPS challenge. Only liver and kidney showed an enhanced level of IL-6 expression in CSF-1-primed mice challenged with LPS, whereas liver, lung, and kidney showed enhanced TNF-α expression. These data indicate that CSF-1 primes tissue MNP but not circulating MNP to transcribe mRNA and release IL-6 and TNF-α. Overall, the data suggest that CSF-11 plays an important role in regulating the sensitivity of the host to the pathophysiological effects of endotoxin.

Original languageEnglish (US)
Pages (from-to)245-252
Number of pages8
JournalJournal of Leukocyte Biology
Volume63
Issue number2
DOIs
StatePublished - Feb 1998
Externally publishedYes

Keywords

  • Endotoxic shock
  • Lipopolysaccharide
  • Macrophages

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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