Effects of human low-density lipoproteins on superoxide production by formyl-methionyl-leucyl-phenylalanine activated polymorphonuclear leukocytes.
Neutrophils play a major role in the host defence by producing reactive oxygen species. These products are liberated by activated cells and are known to cause endothelial cell injury and damage. The present study shows that low-density lipoproteins increase superoxide anion production by twofold in polymorphonuclear leukocytes stimulated by formyl-Met-Leu-Phe in vitro. Moreover, LDL induced a large increase in phosphoinositides and cytosolic-free calcium. Data from experiments performed on neutrophils treated with pertussis toxin, staurosporine, propranolol or niflumic acid suggest that modulation of phospholipase D and A2 activities could be involved in the modification by LDL of leukocyte response to formyl-Met-Leu-Phe. LDL lipid moiety could play a key role in their action on polymorphonuclear functions because cholesterol was exchanged between lipoproteins and cells that can modify membrane fluidity and interact with the formyl-Met-Leu-Phe receptor.
Bonneau
C
C
Laboratoire de Pharmacologie, Unité CNRS 15-35, Hôpital Cochin, Paris, France.
Couderc
R
R
Tissot
M
M
Athias
A
A
Roch-Arveiller
M
M
Giroud
J P
JP
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D002118:Calcium / Q000097:blood; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism*; D009544:Niflumic Acid / Q000494:pharmacology; D037342:Pertussis Toxin; D011433:Propranolol / Q000494:pharmacology; D016897:Respiratory Burst / Q000187:drug effects; D019311:Staurosporine / Q000494:pharmacology; D013481:Superoxides / Q000097:blood*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D008077:Lipoproteins, LDL; D010566:Virulence Factors, Bordetella; D013481:Superoxides; D009544:Niflumic Acid; D009240:N-Formylmethionine Leucyl-Phenylalanine; D002784:Cholesterol; D011433:Propranolol; D037342:Pertussis Toxin; D019311:Staurosporine; D002118:Calcium