Intrapulmonary expression of scavenger receptor and CD14 and their relation to local inflammatory responses to endotoxemia in mice.
This study was first designed to investigate systematically the kinetics of surface expression of scavenger receptors (SRs) and CD14 on alveolar macrophages in vivo and in vitro and their relation with local pro- and antiinflammatory responses in endotoxemia. The expression of SR and CD14 in lungs was down- and up-regulated, respectively, in the presence of endotoxemia, which might be due to decreased expression of SR and increased expression of CD14 on the surface of the resident macrophages. Down-regulation of SRs on alveolar macrophages not only induces decreased defensive function of the macrophages, it also enhances lipopolysaccharide (LPS)-induced activation of alveolar macrophages possibly through increasing LPS binding to CD14. Although CD14 is a key receptor responsible for LPS to activate macrophages, both phospholipase C and anti-CD14 antibody can completely inhibit activation of alveolar macrophages initiated by only LPS 1 ng/ml, as determined by tumor necrosis factor-alpha (TNFalpha) production, but it does not significantly change TNFalpha release upon cell stimulation by LPS 10 microg/ml. There was an intrinsic relation of enhanced intrapulmonary pro- and antiinflammatory responses with changes in SR and CD14 expression, which suggests that the down-regulation of SR and up-regulation of CD14 might be an important mechanism for the lung to change from a defense organ to an effector organ during sepsis.
Jiang
Jian-Xin
JX
Research Institute of Surgery, Daping Hospital, Third Military Medical University, Daping, Chongqing 400042, China. jiangjx@cta.cq.cn
Chen
Yong-Hua
YH
Xie
Guo-Qi
GQ
Ji
Shan-He
SH
Liu
Da-Wei
DW
Qiu
Jun
J
Zhu
Pei-Fang
PF
Wang
Zheng-Guo
ZG
D000818:Animals; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D019446:Endotoxemia / Q000378:metabolism*; D005260:Female; D007150:Immunohistochemistry; D007378:Interleukins / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D008262:Macrophage Activation / Q000502:physiology; D016676:Macrophages, Alveolar / Q000378:metabolism* / Q000502:physiology; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D011971:Receptors, Immunologic / Q000378:metabolism*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D015854:Up-Regulation
D007378:Interleukins; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B