Rat neutrophil function, and leukotriene generation in essential fatty acid deficiency.
Since the essential fatty acid linoleic acid is the precursor of arachidonic acid and thus of leukotrine B4 (LTB4), essential fatty acid deficiency (EFAD) may result in decreased synthesis of this stimulator of neutrophil granulocyte functions. Peritoneal and blood neutrophils from rats fed a diet with only 0.3% of energy requirements as linoleic acid and exhibiting biochemical evidence of EFAD showed substantial functional impairments compared to neutrophils from rats maintained on a diet with 3% of the energy requirement as linoleic acid. Oxidative burst activation (assessed by chemiluminescence), chemotaxis and aggregation were impaired upon stimulation with formylpeptides or the ionophore A23187. In contrast, these functions were intact on stimulation with exogenous LTB4. Chemiluminescence was slightly but not significantly enhanced in EFAD rat neutrophils compared to controls when stimulated with phorbol myristate acetate (PMA). There were no differences between EFAD and control peritoneal neutrophils in the number of f-met-leu-phe (fMLP) receptors, or in their affinity for the ligand, assessed with fML(3H)P. The fraction of responding cells also were similar, assessed with dichlorofluorescein diacetate fluorescence. Moreover, the endogeneous LTB4 production in response to A23187 or fMLP was decreased by 57.7% and 63.5%, respectively, in EFAD peritoneal neutrophils. Thus, EFAD was associated with reductions of LTB4 production and neutrophil responsiveness to A23187 and formylpeptides but not to LTB4 or PMA, which supports the hypothesis that endogeneous LTB4 may contribute to the activation of neutrophil functions involved in inflammation and host defense.
Gyllenhammar
H
H
Department of Medicine 3, Karolinska Institute, Södersjukhuset, Stockholm, Sweden.
Palmblad
J
J
Ringertz
B
B
Hafström
I
I
Borgeat
P
P
D000818:Animals; D002634:Chemotaxis, Leukocyte; D004537:Eicosanoic Acids / Q000032:analysis; D005228:Fatty Acids, Essential / Q000172:deficiency*; D007975:Leukotriene B4 / Q000096:biosynthesis*; D008163:Luminescent Measurements; D008297:Male; D008856:Microscopy, Fluorescence; D009504:Neutrophils / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains
D004537:Eicosanoic Acids; D005228:Fatty Acids, Essential; D007975:Leukotriene B4