Modulatory action of endogenous and exogenous nitric oxide on survival of alveolar macrophages from normal and bleomycin-treated rats.

To investigate the modulatory action of endogenous and exogenous nitric oxide (NO) on survival of alveolar macrophages (AMs) in different cellular states, AMs from normal rats (normal AMs) and from bleomycin (BLM)-treated rats (BLM AMs) were incubated by sodium nitroprusside (SNP, NO donor) and L-arginin (L-Arg, NO precursor), respectively. The survival of AMs was evaluated by apoptosis and cell cycles. The molecular mechanisms were investigated by the contents of Bcl-2, Bax proteins in AMs. The results are as follows: (1) The degree of BLM AMs apoptosis was higher than that of normal AMs; the number of BLM AMs in G(0)/G(1) phases was less than that of normal AMs; there was no significant difference in S+G(2)M phases between the number of BLM AMs and that of normal AMs. (2) Down-regulation of Bcl-2 and up-regulation of Bax occurred in BLM AMs, compared to those in normal AMs. (3) Apoptosis of AMs, either normal AMs or BLM AMs, was induced by both SNP and L-Arg, when compared to their respective control; only the number of BLM AMs in S+G(2)M phases was increased by L-Arg. (4) SNP and L-Arg induced a down-regulation of Bcl-2 and an up-regulation of Bax proteins in normal AMs, but did not induce the same change pattern in BLM AMs. (5) The Bax in BLM AMs was down-regulated by L-Arg. It is concluded that NO can induce the apoptosis of BLM AMs and normal AMs; that Bcl-2 and Bax are implicated in NO-induced apoptosis of normal AMs, whereas they are not involved in that of BLM AMs, suggesting the differential molecular mechanisms underlying the NO-induced apoptosis of normal AMs and BLM AMs; and that endogenous NO promotes proliferation of BLM AMs, which might be associated with down-regulation of Bax.