Age-related enhancement of 5-lipoxygenase metabolic capacity in cattle alveolar macrophages.
Arachidonic acid (AA) metabolism was assessed in cultured alveolar macrophages (AM) obtained from newborn (9- and 23-day-old) and adult (2- and 6-yr-old) cattle. The AM were prelabeled in [3H]AA-containing medium and, thereafter, stimulated with either A-23187 or zymosan. The released radiolabeled AA metabolites were measured by high-performance liquid chromatography with on-line radiodetection. The results showed that, among different-aged cattle, the synthesis of total 5-lipoxygenase (5-LO) metabolites [leukotrienes (LT) B4, LTC4, LTD4, and 5-hydroxyeicosatetraenoic acid (5-HETE)] increased with age in spite of similar levels of phospholipase-catalyzed AA release. In response to A-23187 and zymosan, 5-LO metabolic capacity of adult cattle AM was approximately 4- and approximately 10-fold that of 9-day-old cattle AM, respectively. As 5-LO metabolic capacity increased, the release of prostaglandins and thromboxane tended to decrease. Immunoblot analysis showed that the steady-state expression of 5-LO and 5-lipoxygenase-activating protein (FLAP) also increased in an age-dependent manner. In newborn calves, AM do not produce great amounts of LTB4; this factor might contribute to insufficient polymorphonuclear leukocyte recruitment into the alveolar space and the high susceptibility to neonatal lung infection.
Department of Physiology, Michigan State University, East Lansing 48824, USA.
M C
MC
Lu
M
M
Peters-Golden
D E
DE
Hostetler
N E
NE
Robinson
F J
FJ
Derksen
D058927:5-Lipoxygenase-Activating Proteins; D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D016718:Arachidonic Acid / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D000001:Calcimycin / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D002417:Cattle; D005260:Female; D008262:Macrophage Activation; D016676:Macrophages, Alveolar / Q000201:enzymology*; D008565:Membrane Proteins / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D015054:Zymosan
D058927:5-Lipoxygenase-Activating Proteins; D002352:Carrier Proteins; D008565:Membrane Proteins; D016718:Arachidonic Acid; D000001:Calcimycin; D015054:Zymosan; D001094:Arachidonate 5-Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases