TY - JOUR
T1 - Hemoprotein-dependent production of a neutrophil-activating factor from arachidonic acid
AU - Wallace, J. L.
AU - Rioux, K. P.
AU - McKnight, W.
AU - Carter, L.
AU - Jourd'Heuil, D.
AU - Meddings, J.
AU - Zimmerman, B. J.
AU - Granger, D. N.
AU - Grisham, M. B.
PY - 1992
Y1 - 1992
N2 - Hemoproteins have been suggested to contribute to various forms of tissue injury by catalyzing the peroxidation of lipids. In this study, the ability of hemoglobin to catalyze the production of a neutrophil-activating factor from arachidonic acid was examined. Incubation of arachidonic acid, hydrogen peroxide, and hemoglobin at 37°C for 30 min resulted in the production of a lipid-extractable substance that was chemotactic for neutrophils in vitro and could stimulate leukocyte adherence in vivo. These actions could be inhibited by two leukotriene B4 (LTB4) receptor antagonists. The peroxidation product cross-reacted significantly with an antibody directed against LTB4, but not with an antibody directed against LTC4. The production of this factor was hemoprotein dependent. Immunoreactive LTB4 and biological activity were produced only when hemoglobin, or another hemoprotein, cytochrome c, was present in the reaction mixture. The amount of the factor produced could be increased in a concentration-dependent manner by increasing the amounts of arachidonic acid or hydrogen peroxide in the reaction mixture. The production of this factor could be inhibited by 5-aminosalicylic acid, catalase, or deferoxamine. Separation of the lipid-extractable products of the peroxidation of arachidonic acid on high-performance liquid chromatography revealed that the immunoreactive (with anti-LTB4) and chemotactic substance had a retention time distinct from that of LTB4 and the hydroxy- eicosatetraenoic acids. A lipid-extractable substance with significant cross- reactivity to anti-LTB4 could also be produced if plasma was substituted for arachidonic acid in the reaction mixture. These studies demonstrate that a neutrophil-activating factor with immunoreactivity and biological activity similar to LTB4 can be produced through hemoprotein-dependent peroxidation of arachidonic acid. The production of such a factor at sites of inflammation may contribute to activation and recruitment of neutrophils, and may contribute to the well-documented ability of hemoproteins to exacerbate tissue injury.
AB - Hemoproteins have been suggested to contribute to various forms of tissue injury by catalyzing the peroxidation of lipids. In this study, the ability of hemoglobin to catalyze the production of a neutrophil-activating factor from arachidonic acid was examined. Incubation of arachidonic acid, hydrogen peroxide, and hemoglobin at 37°C for 30 min resulted in the production of a lipid-extractable substance that was chemotactic for neutrophils in vitro and could stimulate leukocyte adherence in vivo. These actions could be inhibited by two leukotriene B4 (LTB4) receptor antagonists. The peroxidation product cross-reacted significantly with an antibody directed against LTB4, but not with an antibody directed against LTC4. The production of this factor was hemoprotein dependent. Immunoreactive LTB4 and biological activity were produced only when hemoglobin, or another hemoprotein, cytochrome c, was present in the reaction mixture. The amount of the factor produced could be increased in a concentration-dependent manner by increasing the amounts of arachidonic acid or hydrogen peroxide in the reaction mixture. The production of this factor could be inhibited by 5-aminosalicylic acid, catalase, or deferoxamine. Separation of the lipid-extractable products of the peroxidation of arachidonic acid on high-performance liquid chromatography revealed that the immunoreactive (with anti-LTB4) and chemotactic substance had a retention time distinct from that of LTB4 and the hydroxy- eicosatetraenoic acids. A lipid-extractable substance with significant cross- reactivity to anti-LTB4 could also be produced if plasma was substituted for arachidonic acid in the reaction mixture. These studies demonstrate that a neutrophil-activating factor with immunoreactivity and biological activity similar to LTB4 can be produced through hemoprotein-dependent peroxidation of arachidonic acid. The production of such a factor at sites of inflammation may contribute to activation and recruitment of neutrophils, and may contribute to the well-documented ability of hemoproteins to exacerbate tissue injury.
KW - 5- aminosalicylic acid
KW - adherence
KW - chemotaxis
KW - hemoglobin
KW - leukocyte
KW - leukotriene
KW - peroxidation
UR - http://www.scopus.com/inward/record.url?scp=0026465120&partnerID=8YFLogxK
U2 - 10.1152/ajpheart.1992.263.5.h1546
DO - 10.1152/ajpheart.1992.263.5.h1546
M3 - Journal Article
C2 - 1332515
AN - SCOPUS:0026465120
SN - 0002-9513
VL - 263
SP - H1546-H1553
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 5 32-5
ER -