Macrophage-derived cytokines may provoke the inflammatory response in lung injury. Because macrophage influx is a prominent feature of the cellular inflammatory response accompanying the development of bronchopulmonary dysplasia, we hypothesized that blocking macrophage influx would reduce overall cellular influx and oxidative damage. Newborn rats were exposed at birth to 95% O(2) or air for 1 wk, and hyperoxia-exposed pups were injected with anti-monocyte chemoattractant protein-1 (MCP-1) or IgG control on days 3-5. MCP-1 was increased in bronchoalveolar lavage fluid and in histological sections from the 95% O(2)-exposed, IgG-injected pups compared with air-exposed controls. At 1 wk, anti-MCP-1-treated pups had reduced leukocyte numbers, both macrophages and neutrophils, in bronchoalveolar lavage fluid compared with IgG-treated controls. Cytokine-induced neutrophil chemoattractant-1, the rat analog of IL-8, was not significantly decreased in lavage fluid but was reduced in lung cells in anti-MCP-1-treated pups. Tissue carbonyls, a measure of protein oxidation, were decreased in anti-MCP-1-treated pups. Anti-MCP-1 treatment prevented neutrophil influx and reduced protein oxidation in hyperoxia-exposed newborn rats.

The aims of this study were to determine regional differences and the mechanism of gastric contractile effects of erythromycin. Rabbit gastric circular muscle strips were studied in vitro. The threshold dose for erythromycin was significantly less and the maximum contraction greater in the antrum (1 microM and 0.9 +/- 0.3 kg/cm2) than in the fundus (10 microM and 0.3 +/- 0.1 kg/cm2). Erythromycin-induced antral contractions were decreased by motilin tachyphylaxis but unaffected by tetrodotoxin, atropine, hexamethonium, or ondansetron. At a subthreshold dose (0.1 microM), erythromycin increased the frequency, but not the amplitude, of bethanechol (10 +/- 3%)-and substance P-induced (13 +/- 5%) phasic antral contractions. This chronotropic effect was inhibited with tetrodotoxin, atropine, or motilin tachyphylaxis. Erythromycin (10 microM) and motilin (1 microM) enhanced the amplitude of substance P-induced tonic fundic contractions by 38 and 32%, respectively, without effect on bethanechol-induced contractions. In summary, erythromycin contracts antral muscle more potently and forcefully than fundic muscle. Erythromycin increases antral contractility by two mechanisms: an inotropic effect acting on smooth muscle motilin receptors, and, at lower doses, a cholinergic chronotropic effect mediated through neuronal motilin receptors.

No abstract