AJP - Lung Cellular and Molecular Physiology, Vol 268, Issue 2 294-L301, Copyright © 1995 by American Physiological Society
Expression and role of cyclooxygenase isoforms in alveolar and peritoneal macrophages
J. Wilborn, D. L. DeWitt and M. Peters-Golden
Department of Internal Medicine, University of Michigan, Ann Arbor.
Prostaglandin synthesis represents one means by which macrophages modulate
inflammation. The initial enzyme in the metabolism of arachidonic acid to
prostaglandins is cyclooxygenase (COX). Both constitutive (COX-1) and
inducible (COX-2) isoforms are recognized. We previously showed that COX
activity of rat peritoneal macrophages (PM) exceeds that of alveolar
macrophages (AM). In this study, we correlated the steady-state levels of
COX-1 and COX-2 proteins with COX activity in resident AM and PM. Freshly
obtained AM contained lower levels of COX-1 than did fresh PM. Neither
contained substantial amounts of COX-2 in the basal state, but both cell
types demonstrated induction when cultured with lipopolysaccharide; once
again, COX-2 levels in PM exceeded those in AM. Despite COX-2 induction
under these circumstances, its contribution to prostaglandin production
appeared to be modest. We conclude that, although both isoforms of COX are
expressed in rat AM and PM, COX-1 is responsible for the majority of enzyme
activity in both the basal and stimulated states. The lesser prostaglandin
synthetic capacity of AM than of PM appears to be the consequence of lower
steady-state levels of both COX proteins.
