Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 191, Issue 7, Pages 1197-1207Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.191.7.1197
Keywords
inhibitory receptors; antiinflammation; resolution; leukocytes; MHC binding peptide
Categories
Funding
- NIDDK NIH HHS [DK50305] Funding Source: Medline
- NIGMS NIH HHS [GM38765] Funding Source: Medline
Ask authors/readers for more resources
Lipoxin (LX) A(4) and aspirin-triggered LX (ATL) are endogenous lipids that regulate leukocyte trafficking via specific LXA(4) receptor (ALXRs) and mediate antiinflammation and resolution ATL analogues dramatically inhibited human neutrophil (polymorphonuclear leukocyte [PMN]) responses evoked by a potent necrotactic peptide derived from mitochondria as well as a rogue synthetic chemotactic peptide. These bioactive lipid analogues and small peptides each selectively competed for specific (3)H-LXA(4) binding with recombinant human ALXR, and its N-glycosylation proved essential for peptide but not LXA(4) recognition. Chimeric receptors constructed from receptors with opposing functions, namely ALXR and leukotriene B(4) receptors (BLTs), revealed that the seventh transmembrane segment and adjacent regions of ALXR are essential for LXA(4) recognition, and additional regions of ALXR are required for high affinity binding of the peptide ligands. Together, these findings are the first to indicate that a single Seven-transmembrane receptor san switch recognition as well as function with certain chemotactic peptides to inhibitory with ATL and LX (lipid ligands). Moreover, they suggest that ALXR activation by LX or ATL can protect the host from potentially deleterious PMN responses associated with innate immunity as well as direct effector responses in tissue injury by recognition of peptide fragments.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available