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CSF‐1 (M‐CSF) differentially sensitizes mononuclear phagocyte subpopulations to endotoxin in vivo: a potential pathway that regulates the severity of Gram‐negative infections
Author(s) -
Chapoval Andrei I.,
Kamdar Sonya J.,
Kremlev Sergey G.,
Evans Robert
Publication year - 1998
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.63.2.245
Subject(s) - spleen , lipopolysaccharide , tumor necrosis factor alpha , in vivo , biology , mononuclear phagocyte system , peripheral blood mononuclear cell , intraperitoneal injection , cytokine , immunology , kidney , medicine , endocrinology , in vitro , biochemistry , microbiology and biotechnology
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‐1 plays an important role in regulating the sensitivity of the host to the pathophysiological effects of endotoxin. J. Leukoc. Biol . 63: 245–252; 1998.