PMID- 10092806
OWN - NLM
STAT- MEDLINE
DCOM- 19990413
LR  - 20181201
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 162
IP  - 6
DP  - 1999 Mar 15
TI  - A novel receptor tyrosine kinase, Mer, inhibits TNF-alpha production and
      lipopolysaccharide-induced endotoxic shock.
PG  - 3498-503
AB  - The regulation of monocyte function and the inhibition of TNF-alpha production
      during bacterial sepsis are critical in attenuating adverse host responses to
      endotoxemia. To study the function of a novel receptor tyrosine kinase, mer, that
      is expressed in monocytes, we generated mice (merkd) that lack the signaling
      tyrosine kinase domain. Upon LPS challenge, merkd animals died of endotoxic shock
      (15/17, 88.2%), whereas control wild-type mice survived (1/15, 6.7% died).
      Susceptible merkd mice exhibited edema, leukocyte infiltration, and signs of
      endotoxic shock that correlated with higher levels of TNF-alpha found in the
      serum of merkd mice as compared with wild-type control animals. Death due to
      LPS-induced endotoxic shock in merkd mice was blocked by administration of
      anti-TNF-alpha Ab, suggesting that overproduction of this cytokine was
      principally responsible for the heightened suseptibility. The increase in
      TNF-alpha production appeared to be the result of a substantial increase in the
      LPS-dependent activation of NF-kappa B nuclear translocation resulting in greater
      TNF-alpha production by macrophages from merkd mice. Thus, Mer receptor tyrosine 
      kinase signaling participates in a novel inhibitory pathway in macrophages
      important for regulating TNF-alpha secretion and attenuating endotoxic shock.
FAU - Camenisch, T D
AU  - Camenisch TD
AD  - Department of Microbiology and Immunology, University of North Carolina, Chapel
      Hill 27599, USA.
FAU - Koller, B H
AU  - Koller BH
FAU - Earp, H S
AU  - Earp HS
FAU - Matsushima, G K
AU  - Matsushima GK
LA  - eng
GR  - P01-DK 38103/DK/NIDDK NIH HHS/United States
GR  - R01-CA68346/CA/NCI NIH HHS/United States
GR  - R29-NS35372/NS/NINDS NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Neural Cell Adhesion Molecules)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.10.1 (Mertk protein, mouse)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (c-Mer Tyrosine Kinase)
SB  - AIM
SB  - IM
MH  - Animals
MH  - Crosses, Genetic
MH  - Drug Resistance/genetics
MH  - Lipopolysaccharides/*toxicity
MH  - Macrophages/metabolism
MH  - Mice
MH  - Mice, Inbred DBA
MH  - Mice, Knockout
MH  - Neural Cell Adhesion Molecules/genetics/metabolism/*physiology
MH  - *Proto-Oncogene Proteins
MH  - Receptor Protein-Tyrosine Kinases/genetics/metabolism/*physiology
MH  - Sepsis/immunology/mortality/prevention & control
MH  - Shock, Septic/etiology/genetics/*prevention & control
MH  - Tumor Necrosis Factor-alpha/*antagonists & inhibitors/*biosynthesis/metabolism
MH  - c-Mer Tyrosine Kinase
EDAT- 1999/03/27 00:00
MHDA- 1999/03/27 00:01
CRDT- 1999/03/27 00:00
PHST- 1999/03/27 00:00 [pubmed]
PHST- 1999/03/27 00:01 [medline]
PHST- 1999/03/27 00:00 [entrez]
PST - ppublish
SO  - J Immunol. 1999 Mar 15;162(6):3498-503.