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Targeted disruption of the leukotriene B(4) receptor in mice reveals its role in inflammation and platelet-activating factor-induced anaphylaxis.

Publication ,  Journal Article
Haribabu, B; Verghese, MW; Steeber, DA; Sellars, DD; Bock, CB; Snyderman, R
Published in: J Exp Med
August 7, 2000

Leukotrienes are derived from arachidonic acid and serve as mediators of inflammation and immediate hypersensitivity. Leukotriene B(4) (LTB(4)) and leukotriene C(4) (LTC(4)) act through G protein-coupled receptors LTB(4) 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 LTB(4) for calcium mobilization or chemotaxis. Additionally, LTB(4) elicited peritoneal neutrophil influx in control but not in BLTR(-/-) mice. Thus, BLTR is the sole receptor for LTB(4)-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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Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

August 7, 2000

Volume

192

Issue

3

Start / End Page

433 / 438

Location

United States

Related Subject Headings

  • Zymosan
  • Receptors, Leukotriene B4
  • Platelet Activating Factor
  • Peritoneum
  • Neutrophils
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Macrophages, Peritoneal
 

Citation

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Haribabu, B., Verghese, M. W., Steeber, D. A., Sellars, D. D., Bock, C. B., & Snyderman, R. (2000). Targeted disruption of the leukotriene B(4) receptor in mice reveals its role in inflammation and platelet-activating factor-induced anaphylaxis. J Exp Med, 192(3), 433–438. https://doi.org/10.1084/jem.192.3.433
Haribabu, B., M. W. Verghese, D. A. Steeber, D. D. Sellars, C. B. Bock, and R. Snyderman. “Targeted disruption of the leukotriene B(4) receptor in mice reveals its role in inflammation and platelet-activating factor-induced anaphylaxis.J Exp Med 192, no. 3 (August 7, 2000): 433–38. https://doi.org/10.1084/jem.192.3.433.
Haribabu B, Verghese MW, Steeber DA, Sellars DD, Bock CB, Snyderman R. Targeted disruption of the leukotriene B(4) receptor in mice reveals its role in inflammation and platelet-activating factor-induced anaphylaxis. J Exp Med. 2000 Aug 7;192(3):433–8.
Haribabu, B., et al. “Targeted disruption of the leukotriene B(4) receptor in mice reveals its role in inflammation and platelet-activating factor-induced anaphylaxis.J Exp Med, vol. 192, no. 3, Aug. 2000, pp. 433–38. Pubmed, doi:10.1084/jem.192.3.433.
Haribabu B, Verghese MW, Steeber DA, Sellars DD, Bock CB, Snyderman R. Targeted disruption of the leukotriene B(4) receptor in mice reveals its role in inflammation and platelet-activating factor-induced anaphylaxis. J Exp Med. 2000 Aug 7;192(3):433–438.

Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

August 7, 2000

Volume

192

Issue

3

Start / End Page

433 / 438

Location

United States

Related Subject Headings

  • Zymosan
  • Receptors, Leukotriene B4
  • Platelet Activating Factor
  • Peritoneum
  • Neutrophils
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Macrophages, Peritoneal