PMID- 10644052
OWN - NLM
STAT- MEDLINE
DCOM- 20000203
LR  - 20190623
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 59
IP  - 4
DP  - 2000 Feb 15
TI  - Biological actions of the free acid of hepoxilin A3 on human neutrophils.
PG  - 435-40
AB  - In earlier reports and reviews, it was suggested that unlike its methyl ester, 
      the free acid form of the 12-lipoxygenase-derived eicosanoid hepoxilin A3 (HXA3) 
      does not enter neutrophils and other cells. Therefore, in the past, most studies 
      on the biological activities of HXA3 on human neutrophils were conducted with its 
      methyl ester. Here, we present evidence that free HXA3 is biologically active 
      towards human neutrophils at submicromolar concentrations, which may occur under 
      certain circumstances in vivo. Thus, HXA3 caused chemotaxis at concentrations as 
      low as 30-40 nM, an effect which was attenuated at higher concentrations of this 
      eicosanoid. Its chemotactic potency proved to be comparable to that of 
      leukotriene B4, but higher than that of the chemotactic peptide 
      formyl-methionyl-leucyl-phenylalanine (fMLP), and greatly exceeded that of the 
      other 12-lipoxygenase metabolite, 12(S)-hydroxy-5,8,10,14-eicosatetraenoic acid, 
      which was inactive at comparable concentrations. The chemotactic activity of HXA3 
      was not abolished by serum albumin, but it was suppressed by pertussis toxin. 
      Unlike fMLP, at this concentration range HXA3 did not cause respiratory burst or 
      aggregation of the neutrophils or activation of protein kinase C. These 
      observations suggest a remarkably selective and specific receptor-mediated 
      process. At concentrations higher than 1 microM, HXA3 gives rise to an 
      instantaneous release of calcium from intracellular stores which causes, however, 
      only a slight, if any, liberation of arachidonic acid. On the other hand, 
      pretreatment of the neutrophils with submicromolar concentrations of HXA3 
      significantly blunts the liberation of arachidonic acid caused by fMLP.
FAU - Sutherland, M
AU  - Sutherland M
AD  - Department of Gynaecology, University Medical Centre Benjamin Franklin, Free 
      University of Berlin, Germany.
FAU - Schewe, T
AU  - Schewe T
FAU - Nigam, S
AU  - Nigam S
LA  - eng
PT  - Journal Article
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 127128-05-6 (11-glutathionylhepoxilin A3)
RN  - 27YG812J1I (Arachidonic Acid)
RN  - FC398RK06S (8,11,14-Eicosatrienoic Acid)
SB  - IM
MH  - 8,11,14-Eicosatrienoic Acid/*analogs & derivatives/pharmacology
MH  - Arachidonic Acid/metabolism
MH  - Chemotaxis, Leukocyte/*drug effects
MH  - Humans
MH  - In Vitro Techniques
MH  - Neutrophils/*drug effects/metabolism/physiology
MH  - Signal Transduction/drug effects
EDAT- 2000/01/22 00:00
MHDA- 2000/01/22 00:01
CRDT- 2000/01/22 00:00
PHST- 2000/01/22 00:00 [pubmed]
PHST- 2000/01/22 00:01 [medline]
PHST- 2000/01/22 00:00 [entrez]
AID - S0006-2952(99)00345-7 [pii]
AID - 10.1016/s0006-2952(99)00345-7 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2000 Feb 15;59(4):435-40. doi: 10.1016/s0006-2952(99)00345-7.