Unique aspects of the modulation of human neutrophil function by 12-L-hydroperoxy-5,8,10,14-eicosatetraenoic acid

Prostaglandins. 1980 Jan;19(1):71-85. doi: 10.1016/0090-6980(80)90155-0.

Abstract

12-L-hydroperoxy-5,8,10,14-eicosatetraenoic acid (12-OOHETE), a labile intermediate generated by the lipoxygenation of arachidonic acid in platelets, and 12-L-hydroxy-5,8,10.14-eicosatetraenoic acid (12-OHETE), the reduction product of 12-OOHETE, were examined for their effects on human neutrophil function in vitro. 12-OOHETE elicited a maximal neutrophil chemotactic response at 4 microgram/ml, that exceeded by over 50% the maximal chemotactic response to 10-20 microgram/ml of 12-OHETE. Similarly 12-OOHETE was more potent than 12-OHETE in evoking neutrophil chemokinetic responses and in enhancing the expression of C3b receptors on neutrophils. The concentration of guanosine 3':5' cyclic monophosphate (cGMP) in neutrophils was increased to the same plateau level by 5 ng/ml of 12-OOHETE and by 50 ng/ml of 12-OHETE. Elevations in the concentration of cGMP were maintained for 30 min or longer by a single dose of 12-OOHETE, but fell between 10 and 20 min after the introduction of 12-OHETE. The release of neutrophil lysosomal enzymes by the chemotactic fragments of C5 was augmented substantially by 12-OOHETE, while 12-OHETE had only a marginal effect. The non-chemotactic methyl ester of 12-OHETE failed to inhibit the chemotactic responses to 12-OOHETE at molar ratios that suppressed comparable response to 12-OHETE by 42-86%. Thus 12-OOHETE is more potent than 12-OHETE in the stimulation of some human neutrophil functions and in the elevation of the cellular concentration of cGMP. Furthermore, 12-OOHETE may activate neutrophils by pathways not available to 12-OHETE.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
  • Arachidonic Acids / pharmacology*
  • Chemotaxis, Leukocyte / drug effects
  • Complement C3b / immunology
  • Cyclic AMP / metabolism
  • Cyclic GMP / metabolism
  • Glucuronidase / metabolism
  • Humans
  • Leukotrienes*
  • Lipid Peroxides*
  • Neutrophils / drug effects*
  • Neutrophils / enzymology
  • Neutrophils / metabolism
  • Peroxides / pharmacology*
  • Receptors, Complement / immunology
  • Rosette Formation

Substances

  • Arachidonic Acids
  • Leukotrienes
  • Lipid Peroxides
  • Peroxides
  • Receptors, Complement
  • 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
  • 15-hydroperoxy-5,8,11,13-eicosatetraenoic acid
  • Complement C3b
  • Cyclic AMP
  • Glucuronidase
  • Cyclic GMP