C. Delacourt et al., MODULATORY EFFECTS OF PKC ACTIVITY ON INCREASED 92-KDA GELATINASE SECRETION BY NEONATAL ALVEOLAR MACROPHAGES, American journal of physiology. Lung cellular and molecular physiology, 17(5), 1997, pp. 989-996
We previously demonstrated that alveolar macrophages (AMs) from neonat
al rats can secrete more 92-kDa gelatinase than AMs from adult rats. I
n this study, we investigated the role of the protein kinase C (PKC) p
athway in the transductional regulation of 92-kDa gelatinase secretion
by rat AMs, and we also evaluated maturational changes in this role w
ith increasing postnatal age. After AM stimulation by phorbol 12-myris
tate 13-acetate (PMA), we observed a dose-dependent increase in gelati
nase secretion that was significantly more marked in AMs from B-day-ol
d rats than in AMs from adult rats and that was inhibited by the PKC i
nhibitor calphostin C. Adenosine 3',5'-cyclic monophosphate mimetics o
r concanavalin A failed to induce an increase in gelatinase secretion
by AMs. Time-dependent variations in PKC activity after PMA stimulatio
n differed significantly between B-day-old rats and adult rats; PKC ac
tivity decreased in adult AMs (50%) but remained stable in 6-day-old A
Ms. We therefore investigated age-related differences in the intracell
ular proteolytic degradation of PKC, which is thought to be mediated b
y calpains. Leupeptin, used as a calpain inhibitor, inhibited the decr
ease in PKC activity after exposure of adult AMs to PMA and induced a
greater than threefold increase in PMA-induced gelatinase secretion. C
alpain activity was significantly lower in AM extracts from 6-day-old
than from adult rats. The physiological implication of these developme
ntal changes in 92-kDa gelatinase regulation was demonstrated by inves
tigation of AMs from 1-day-old rats that showed a high level of sponta
neous PKC-dependent gelatinase secretion coexisting with very low calp
ain 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.