PMID- 8006586 OWN - NLM STAT- MEDLINE DCOM- 19940721 LR - 20190508 IS - 0022-1007 (Print) IS - 1540-9538 (Electronic) IS - 0022-1007 (Linking) VI - 180 IP - 1 DP - 1994 Jul 1 TI - Identification of a human cDNA encoding a functional high affinity lipoxin A4 receptor. PG - 253-60 AB - Lipoxin A4 (LXA4) triggers selective responses with human neutrophils that are pertussis toxin sensitive and binds to high affinity receptors (Kd = 0.5 +/- 0.3 nM) that are modulated by stable analogues of guanosine 5'-triphosphate (GTP). Here, we characterized [11,12-(3)]LXA4 specific binding with neutrophil granule and plasma membranes, which each display high affinity binding sites (Kd = 0.7 +/- 0.1 nM) that were regulated by GTP gamma S. Since functional LXA4 receptors are inducible in HL-60 cells, we tested orphan cDNAs encoding 7-transmembrane region receptors cloned from these cells for their ability to bind and signal with LXA4. Chinese hamster ovary (CHO) cells transfected with the orphan receptor cDNA (pINF114) displayed specific 3H-LXA4 high affinity binding (1.7 nM). When displacement of LXA4 binding with pINF114-transfected CHO cells was tested with other eicosanoids, including LXB4, leukotriene D4 (LTD4), LTB4, or prostaglandin E2, only LTD4 competed with LXA4, giving a Ki of 80 nM. In transfected CHO cells, LXA4 also stimulated GTPase activity and provoked the release of esterified arachidonate, which proved to be pertussis toxin sensitive. These results indicate that pINF114 cDNA encodes a 7-transmembrane region-containing protein that displays high affinity for 3H-LXA4 and transmits LXA4-induced signals. Together, they suggest that the encoded protein is a candidate for a LXA4 receptor in myeloid cells. FAU - Fiore, S AU - Fiore S AD - Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115. FAU - Maddox, J F AU - Maddox JF FAU - Perez, H D AU - Perez HD FAU - Serhan, C N AU - Serhan CN LA - eng GR - GM-38765/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Exp Med JT - The Journal of experimental medicine JID - 2985109R RN - 0 (DNA, Complementary) RN - 0 (Hydroxyeicosatetraenoic Acids) RN - 0 (Lipoxins) RN - 0 (Receptors, Eicosanoid) RN - 0 (lipoxin A4) RN - 27YG812J1I (Arachidonic Acid) RN - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine) SB - IM MH - Amino Acid Sequence MH - Animals MH - Arachidonic Acid/metabolism MH - CHO Cells MH - Cricetinae MH - DNA, Complementary/*analysis MH - Humans MH - Hydroxyeicosatetraenoic Acids/*metabolism/pharmacology MH - *Lipoxins MH - Molecular Sequence Data MH - N-Formylmethionine Leucyl-Phenylalanine/metabolism/pharmacology MH - Neutrophils/metabolism MH - Receptors, Eicosanoid/*genetics PMC - PMC2191537 EDAT- 1994/07/01 00:00 MHDA- 1994/07/01 00:01 PMCR- 1995/01/01 CRDT- 1994/07/01 00:00 PHST- 1994/07/01 00:00 [pubmed] PHST- 1994/07/01 00:01 [medline] PHST- 1994/07/01 00:00 [entrez] PHST- 1995/01/01 00:00 [pmc-release] AID - 94275379 [pii] AID - 10.1084/jem.180.1.253 [doi] PST - ppublish SO - J Exp Med. 1994 Jul 1;180(1):253-60. doi: 10.1084/jem.180.1.253.