Age-related enhancement of 5-lipoxygenase metabolic capacity in
cattle alveolar macrophages.
Lu, Min-Chi, Marc Peters-Golden, Douglas E. Hostetler, N. Edward
Robinson, and Frederik J. Derksen.
Departments of Physiology and Large Animal Clinical Sciences,
Michigan State University, East Lansing, Michigan 48824 and Division
of Pulmonary and Critical Care Medicine, Department of Internal
Medicine, University of Michigan, Ann Arbor, Michigan 48105
APStracts 3:0095L, 1996.
Arachidonic acid (AA) metabolism was assessed in cultured alveolar
macrophages (AM) obtained from newborn (9-d and 23-d) and adult (2-y
and 6-y) cattle. The AM were prelabeled in [3H]AA-containing medium
and, thereafter, stimulated with either A23187 or zymosan. The
released radiolabeled AA metabolites were measured by HPLC with on
-line radiodetection. The results showed that, among different-aged
cattle, the synthesis of total 5-lipoxygenase (5-LO) metabolites
(leukotrienes B4 (LTB4), LTC4, LTD4, and 5-hydroxyeicosatetraenoic
acid (5-HETE)) increased with age in spite of similar levels of
phospholipase-catalyzed AA release. In response to A23187 and
zymosan, 5-LO metabolic capacity of adult cattle AM was 4- and 10
-fold that of 9-day 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
age-dependently. In newborn calves, AM do not produce great amounts
of LTB4, this factor might contribute to insufficient PMN recruitment
into the alveolar space and the high susceptibility to neonatal lung
infection.
Received 20 December 1995; accepted in final form 7 May 1996.
APS Manuscript Number L374-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 28 June 96