Shock Lipopolysaccharide-Induced Endotoxic Production and a Inhibits TNF-A Novel Receptor Tyrosine Kinase, Mer,
摘要：
The regulation of monocyte function and the inhibition of TNF- a 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 ( mer kd ) that lack the signaling tyrosine kinase domain. Upon LPS challenge, mer kd animals died of endotoxic shock (15/17, 88.2%), whereas control wild-type mice survived (1/15, 6.7% died). Susceptible mer kd mice exhibited edema, leukocyte inltration, and signs of endotoxic shock that correlated with higher levels of TNF- a found in the serum of mer kd mice as compared with wild-type control animals. Death due to LPS-induced endotoxic shock in mer kd mice was blocked by administration of anti-TNF- a Ab, suggesting that overproduction of this cytokine was principally responsible for the heightened suseptibility. The increase in TNF- a production appeared to be the result of a substantial increase in the LPS-dependent activation of NF- k B nuclear translocation resulting in greater TNF- a production by macrophages from mer kd mice. Thus, Mer receptor tyrosine kinase signaling participates in a novel inhibitory pathway in macrophages important for regulating TNF- a secretion and attenuating endotoxic shock. The Journal of Immunology, 1999, 162: 3498–3503.
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年份：
1999
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