Targeted Disruption of the Leukotriene B4Receptor in Mice Reveals Its Role in Inflammation and Platelet-Activating Factor–Induced Anaphylaxis
B Haribabu, MW Verghese, DA Steeber… - The Journal of …, 2000 - rupress.org
B Haribabu, MW Verghese, DA Steeber, DD Sellars, CB Bock, R Snyderman
The Journal of experimental medicine, 2000•rupress.orgLeukotrienes are derived from arachidonic acid and serve as mediators of inflammation and
immediate hypersensitivity. Leukotriene B4 (LTB4) and leukotriene C4 (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 …
immediate hypersensitivity. Leukotriene B4 (LTB4) and leukotriene C4 (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 …
Leukotrienes are derived from arachidonic acid and serve as mediators of inflammation and immediate hypersensitivity. Leukotriene B4 (LTB4) and leukotriene C4 (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.
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