Virus-induced enhancement of arachidonate metabolism by bovine alveolar macrophages in vitro.
Virus infection of alveolar macrophages both in vivo and in vitro has been associated with a variety of changes in cellular function. Some of these changes are identical to the effects that arachidonate-derived mediators, prostaglandins, leukotrienes, and hydroxyeicosatetraenoic acids, have on macrophage function. Virus infection of macrophages has been previously shown to increase the output of some arachidonate metabolites, most notably PGE2. However, the effect of virus infection on arachidonate metabolism in general has not been well described. In our experiments, primary cultures of alveolar macrophages obtained from normal cattle by bronchoalveolar lavage, were infected in vitro with parainfluenza type 3 virus. At days 0 to 4 post-infection (p.i.) these cells were labelled with 3H-arachidonic acid and stimulated with either serum-coated zymosan, the calcium ionophore A23187, or phorbol myristate acetate. The complete spectrum of arachidonate-derived metabolites was determined by reverse-phase high performance liquid chromatography with UV and on-line radiometric monitoring of column eluant. The total output of metabolites of arachidonic acid by virus-infected alveolar macrophages was increased over that of noninfected controls (with all stimuli tested) by day 4 p.i. (P less than or equal to 0.05). The production of metabolites by the cyclooxygenase, 12- and 5-lipoxygenase enzyme systems was significantly increased, as was the release of 3H-arachidonate. The lack of stimulus specificity and the increases in arachidonate release suggest that greater substrate availability, due either to increased phospholipase activity or direct virus-membrane interaction, may be responsible for the virus-induced enhancement of metabolite output.
Laegreid
W W
WW
Department of Veterinary Microbiology, Washington State University, Pullman 99164-7040.
Taylor
S M
SM
Leid
R W
RW
Silflow
R M
RM
Evermann
J R
JR
Breeze
R G
RG
Liggitt
H D
HD
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D000001:Calcimycin; D002417:Cattle; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology; D008297:Male; D010224:Parainfluenza Virus 3, Human / Q000502:physiology; D018184:Paramyxoviridae Infections / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D010743:Phospholipids / Q000378:metabolism; D011650:Pulmonary Alveoli; D013755:Tetradecanoylphorbol Acetate; D014316:Tritium; D015054:Zymosan
D001095:Arachidonic Acids; D010743:Phospholipids; D014316:Tritium; D016718:Arachidonic Acid; D000001:Calcimycin; D015054:Zymosan; D013755:Tetradecanoylphorbol Acetate