Alterations in arachidonic acid metabolism and chemotactic response in polymorphonuclear leukocytes from patients with rheumatoid arthritis.
This study examines the interrelationship between arachidonic acid (AA) metabolism and chemotactic potential of human peripheral blood neutrophils from both normal donors and patients with rheumatoid arthritis (RA). We demonstrate that there is a significant inverse relationship between the neutrophil's metabolic capability to produce [3H]LTB4 in response to ionophore A23187 stimulation versus the cell's chemotactic potential to optimal concentrations (i.e., 20 nM) of the chemotactic peptide f-Met-Leu-Phe as determined by leading front (r = 0.567, p = 0.009), mean depth (r = 0.458, p = 0.042), and population ratio (r = 0.471, p = 0.036) analyses. Subsequent Percoll density gradient studies revealed several RA neutrophil subpopulations exhibiting significantly enhanced (p less than 0.05) [3H] AA metabolism over corresponding density normal cells. Based on these results, we speculate that RA peripheral blood neutrophils have been "processed" to become less chemotactically-responsive yet more metabolically-active cells, and that the increased ability to produce LTB4 through both increased phospholipase A2 and lipoxygenase activities are part of the increased metabolic capabilities of the cell.
Smith
D M
DM
Department of Medicine, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina 27103.
Johnson
J A
JA
Turner
R A
RA
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism* / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000097:blood*; D000001:Calcimycin; D002452:Cell Count / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007975:Leukotriene B4 / Q000096:biosynthesis; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism
D001095:Arachidonic Acids; D007975:Leukotriene B4; D016718:Arachidonic Acid; D000001:Calcimycin; D009240:N-Formylmethionine Leucyl-Phenylalanine