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.
Lu
M C
MC
Department of Physiology, Michigan State University, East Lansing 48824, USA.
Peters-Golden
M
M
Hostetler
D E
DE
Robinson
N E
NE
Derksen
F J
FJ
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