TY - JOUR
T1 - Neutrophil release of arachidonic acid, oxidants, and proteinases
T2 - causally related or independent
AU - Wesley Ely, E.
AU - Seeds, Michael C.
AU - Chilton, Floyd H.
AU - Bass, David A.
N1 - Funding Information:
This work was supportedb y NIH and RO l-A1-10732.
PY - 1995/9/14
Y1 - 1995/9/14
N2 - This investigation examined the concept that arachidonic acid (AA) serves as a second messenger in stimulation of the respiratory burst and degranulation of polymorphonuclear neutrophils (PMN). The main support for this idea is from observations that reagent AA, added to cell suspensions, stimulates the respiratory burst and degranulation and these events are blocked by PLA2 inhibitors. We verified that exogenously-added AA stimulated release of O2-, myeloperoxidase (MPO), and lysozyme (LZ), but this required amounts of AA which approximated the critical micellar concentration. This suggested that such administration of AA might act as an extracellular agonist, similar to particulate stimuli, rather than acting as a second messenger as might occur following mobilization of AA from cellular membranes. To investigate the role of fatty acids released by hydrolysis of cellular phospholipids, exogenously-added group I, II or III PLA2's were used to mobilize fatty acids from cellular membranes. Mole quantities of cell-associated free fatty acids were measured by negative ion chemical ionization gas chromatography/mass spectrometry. AA mobilization in response to exogenous PLA2 was dose-(0.1 to 10 U/ml PLA2) and time-dependent (peak at 1 to 2 min with a reduction by 4 min). Resting neutrophils contained < 10 pmol free AA/107 PMN; the receptor-mediated agonist N-formyl-methionyl-leucyl-phenylalanine (fMLP) alone did not increase these values. Exogenously-added PLA2 generated large quantities of free AA in control and fMLP-treated cells (462 ± 122 and 2097 ± 176 pmol/107 PMN, respectively); however, this did not induce O2-, nor did it augment the level of O2- stimulated by fMLP. Also, PLA2 caused no degranulation and did not alter degranulation induced by fMLP. PLA2 also did not alter O2- or degranulation responses in primed PMN. The data indicate that mobilization of AA from cellular phospholipids neither stimulates nor modulates the respiratory burst or degranulation of PMN.
AB - This investigation examined the concept that arachidonic acid (AA) serves as a second messenger in stimulation of the respiratory burst and degranulation of polymorphonuclear neutrophils (PMN). The main support for this idea is from observations that reagent AA, added to cell suspensions, stimulates the respiratory burst and degranulation and these events are blocked by PLA2 inhibitors. We verified that exogenously-added AA stimulated release of O2-, myeloperoxidase (MPO), and lysozyme (LZ), but this required amounts of AA which approximated the critical micellar concentration. This suggested that such administration of AA might act as an extracellular agonist, similar to particulate stimuli, rather than acting as a second messenger as might occur following mobilization of AA from cellular membranes. To investigate the role of fatty acids released by hydrolysis of cellular phospholipids, exogenously-added group I, II or III PLA2's were used to mobilize fatty acids from cellular membranes. Mole quantities of cell-associated free fatty acids were measured by negative ion chemical ionization gas chromatography/mass spectrometry. AA mobilization in response to exogenous PLA2 was dose-(0.1 to 10 U/ml PLA2) and time-dependent (peak at 1 to 2 min with a reduction by 4 min). Resting neutrophils contained < 10 pmol free AA/107 PMN; the receptor-mediated agonist N-formyl-methionyl-leucyl-phenylalanine (fMLP) alone did not increase these values. Exogenously-added PLA2 generated large quantities of free AA in control and fMLP-treated cells (462 ± 122 and 2097 ± 176 pmol/107 PMN, respectively); however, this did not induce O2-, nor did it augment the level of O2- stimulated by fMLP. Also, PLA2 caused no degranulation and did not alter degranulation induced by fMLP. PLA2 also did not alter O2- or degranulation responses in primed PMN. The data indicate that mobilization of AA from cellular phospholipids neither stimulates nor modulates the respiratory burst or degranulation of PMN.
KW - Arachidonic acid
KW - Neutrophil
KW - Phospholipase
KW - Respiratory burst
KW - Second messenger
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U2 - 10.1016/0005-2760(95)00110-X
DO - 10.1016/0005-2760(95)00110-X
M3 - Article
C2 - 7548176
AN - SCOPUS:0029111788
SN - 0005-2760
VL - 1258
SP - 135
EP - 144
JO - Biochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism
JF - Biochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism
IS - 2
ER -