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Am J Physiol Lung Cell Mol Physiol 273: L989-L996, 1997;
1040-0605/97 $5.00
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AJP - Lung Cellular and Molecular Physiology, Vol 273, Issue 5 989-L996, Copyright © 1997 by American Physiological Society

ARTICLES

Modulatory effects of PKC activity on increased 92-kDa gelatinase secretion by neonatal alveolar macrophages

C. Delacourt, P. Rouet-Benzineb, C. Delclaux, J. L'Hour, A. Harf and C. Lafuma
Unite de Physiologie Respiratoire, Institut National de la Sante et de la Recherche Medicale Unite 296, Creteil, France.

We previously demonstrated that alveolar macrophages (AMs) from neonatal rats can secrete more 92-kDa gelatinase than AMs from adult rats. In this study, we investigated the role of the protein kinase C (PKC) pathway in the transductional regulation of 92-kDa gelatinase secretion by rat AMs, and we also evaluated maturational changes in this role with increasing postnatal age. After AM stimulation by phorbol 12-myristate 13-acetate (PMA), we observed a dose-dependent increase in gelatinase secretion that was significantly more marked in AMs from 6-day-old rats than in AMs from adult rats and that was inhibited by the PKC inhibitor calphostin C. Adenosine 3',5'-cyclic monophosphate mimetics or concanavalin A failed to induce an increase in gelatinase secretion by AMs. Time-dependent variations in PKC activity after PMA stimulation differed significantly between 6-day-old rats and adult rats; PKC activity decreased in adult AMs (50%) but remained stable in 6-day-old AMs. We therefore investigated age-related differences in the intracellular proteolytic degradation of PKC, which is thought to be mediated by calpains. Leupeptin, used as a calpain inhibitor, inhibited the decrease in PKC activity after exposure of adult AMs to PMA and induced a greater than threefold increase in PMA-induced gelatinase secretion. Calpain activity was significantly lower in AM extracts from 6-day-old than from adult rats. The physiological implication of these developmental changes in 92-kDa gelatinase regulation was demonstrated by investigation of AMs from 1-day-old rats that showed a high level of spontaneous PKC-dependent gelatinase secretion coexisting with very low calpain activity. We conclude that sustained PKC activity is a key factor in the increased gelatinase secretion by AMs seen during the postnatal period and is due, at least in part, to reduced PKC degradation.


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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
M.-L. Franco, P. Waszak, G. Banalec, M. Levame, C. Lafuma, A. Harf, and C. Delacourt
Pre- and Postnatal Lung Development, Maturation, and Plasticity: LPS-induced lung injury in neonatal rats: changes in gelatinase activities and consequences on lung growth
Am J Physiol Lung Cell Mol Physiol, March 1, 2002; 282(3): L491 - L500.
[Abstract] [Full Text] [PDF]


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