TY - JOUR
T1 - CSF-1 (M-CSF) differentially sensitizes mononuclear phagocyte subpopulations to endotoxin in vivo
T2 - A potential pathway that regulates the severity of gram-negative infections
AU - Chapoval, Andrei I.
AU - Kamdar, Sonya J.
AU - Kremlev, Sergey G.
AU - Evans, Robert
PY - 1998/2
Y1 - 1998/2
N2 - 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.
AB - 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.
KW - Endotoxic shock
KW - Lipopolysaccharide
KW - Macrophages
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U2 - 10.1002/jlb.63.2.245
DO - 10.1002/jlb.63.2.245
M3 - Article
C2 - 9468283
AN - SCOPUS:0031882076
SN - 0741-5400
VL - 63
SP - 245
EP - 252
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 2
ER -