Targeted disruption of the leukotriene B4 receptor in mice reveals its role in inflammation and platelet-activating factor-induced anaphylaxis

被引:144
作者
Haribabu, B
Verghese, MW
Steeber, DA
Sellars, DD
Bock, CB
Snyderman, R
机构
[1] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA
[2] Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA
[3] Duke Univ, Med Ctr, Dept Genet, Durham, NC 27710 USA
关键词
arachidonic acid; neutrophil influx; knock-out; sex-related; chemotaxis;
D O I
10.1084/jem.192.3.433
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Leukotrienes are derived from arachidonic acid and sen-e as mediators inflammation and immediate hypersensitivity. Leukotriene B-4 (LTB4) and leukotriene C-4 (LTC4) act through G protein-coupled receptors LTB4 receptor (BLTR) and Cys-LTR, respectively. To investigate the physiological role of BLTR, we produced mice with a targeted disruption of the BLTR gene. Mice deficient for BLTR (BLTR-/-) developed normally and had no apparent hematopoietic abnormalities. Peritoneal neutrophils from BLTR-/- mice displayed normal responses to the inflammatory mediators C5a and platelet-activating factor (PAF) but did not respond to LTB4 for calcium mobilization or chemotaxis. Additionally, LTB4 elicited peritoneal neutrophil influx in control but not in BLTR-/- mice. Thus, BLTR is the sole receptor for LTB4-induced inflammation in mice. Neutrophil influx in a peritonitis model and acute ear inflammation in response to arachidonic acid was significantly reduced in BLTR-/- mice. In mice, intravenous administration of PAF induces immediate lethal anaphylaxis. Surprisingly, female BLTR-/- mice displayed selective survival (6 of 9; P = 0.002) relative to male (1 of 11) mice of PAF-induced anaphylaxis. These results demonstrate the role of BLTR in leukotriene-mediated acute inflammation and an unexpected sex-related involvement in PAF-induced anaphylaxis.
引用
收藏
页码:433 / 438
页数:6
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