Tag: LTB4

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BLTR mediates leukotriene B(4)-induced chemotaxis and adhesion and plays a dominant role in eosinophil accumulation in a murine model of peritonitis.

Leukotriene B(4) (LTB(4)) is a potent chemoattractant active on multiple leukocytes, including neutrophils, macrophages, and eosinophils, and is implicated in the pathogenesis of a variety of inflammatory processes. A seven transmembrane-spanning, G protein-coupled receptor, called BLTR (LTB(4) receptor), has recently been identified as an LTB(4) receptor. To determine if BLTR is the sole receptor mediating LTB(4)-induced leukocyte activation and to determine the role of LTB(4) and BLTR in regulating leukocyte function in inflammation in vivo, we generated a BLTR-deficient mouse by targeted gene disruption. This mouse reveals that BLTR alone is responsible for LTB(4)-mediated leukocyte calcium flux, chemotaxis, and firm adhesion to endothelium in vivo. Furthermore, despite the apparent functional redundancy with other chemoattractant-receptor pairs in vitro, LTB(4) and BLTR play an important role in the recruitment and/or retention of leukocytes, particularly eosinophils, to the inflamed peritoneum in vivo. These studies demonstrate that BLTR is the key receptor that mediates LTB(4)-induced leukocyte activation and establishes a model to decipher the functional roles of BLTR and LTB(4) in vivo.

http://jem.rupress.org/content/192/3/439.long

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Neutrophil Chemotactic Activity of Sputum From Patients With COPD

Neutrophilic inflammation is a major feature of COPD.  Several factors in bronchial secretions have been identified as chemoattractants for neutrophils. The present study was designed to assess the contribution of interleukin (IL)-8 and leukotriene B4 (LTB4) to neutrophil chemotaxis evoked by sputum obtained from patients with established COPD.
Design: Sputum supernatant of 20 patients with COPD was used as chemoattractant in a 96-well
chemotaxis chamber, with subsequent quantification of migrated cells by a luminescence assay.
The contribution of IL-8 and LTB4 to chemotaxis was determined by addition of a neutralizing
antibody and a selective receptor antagonist, respectively.
Measurements and results: COPD sputum caused neutrophil chemotaxis in a concentration dependent manner, with a maximum response evoked with a 10-fold dilution of the original
sample. Pretreatment of sputum or neutrophils with either an anti–IL-8 antibody or the LTB4
antagonist, SB 201146, led to a concentration-dependent inhibition of sputum-induced neutrophil chemotaxis, with a maximum suppression (mean  SEM) of 29.2  4.9% (p < 0.001) from baseline by 100 ng/mL of anti–IL-8 antibody, and 45.6  7% (p < 0.02) by 10 mol/L of SB
201146. The combination of the anti–IL-8 antibody and SB 201146 inhibited neutrophil
chemotaxis, but this was not significantly greater than the effect of SB 201146 or anti–IL-8 alone.
Conclusions: These data confirm the importance of IL-8 and LTB4 as chemoattractants for
neutrophils in bronchial secretions from patients with COPD, and suggest that specific inhibitors
may have therapeutic potential in COPD.

http://journal.publications.chestnet.org/article.aspx?articleid=1081469