Effect of erythromycin on endotoxin-induced microvascular leakage in the rat trachea and lungs.

Abstract

To determine whether the macrolide antibiotic erythromycin prevents microvascular leakage produced by lipopolysaccharide (LPS), we studied tracheae and lungs of pathogen-free rats. Tracheal vascular permeability and neutrophil recruitment were assessed by the percent area occupied by Monastral blue-labeled blood vessels and by myeloperoxidase-containing granulocytes, respectively, in tracheal whole mounts. Pulmonary microvascular leakage was evaluated by lung wet-to-dry (W/D) weight ratio. Inhalation of Escherichia coli LPS (5 mg/kg) caused time-dependent increases in tracheal vascular permeability, neutrophil influx, and lung W/D ratio. These responses were inhibited by pretreatment with oral erythromycin, but not by ampicillin or cefaclor, in a dose-dependent manner: erythromycin at 10 mg/kg daily for 1 wk reduced the area density of Monastral blue-labeled vessels from 6.7 +/- 1.2 to 1.4 +/- 0.3% (p < 0.01), the number of neutrophils (from 365 +/- 51 to 149 +/- 30 cells/mm2, p < 0.01), and lung W/D weight ratio (from 6.76 +/- 0.30 to 5.39 +/- 0.21, p < 0.01). This inhibitory effect of erythromycin was abolished by depletion of circulating neutrophils with cyclophosphamide. These results suggest that LPS causes acute lung injury, microvascular leakage, and neutrophil recruitment in the trachea, and that erythromycin protects against these changes, probably by acting on neutrophils.

Untitled

“…Increased capillary permeability has been described after intratracheal administration of LPS and HCl in rats (23,26). Also in our experiments, both inflammatory stimuli promoted an increase in capillary permeability as well as SSL localization.…”

“…LPS, a component of the Gram-negative bacterial cell wall, has been shown to increase capillary permeability in lung tissue after local administration (26). To test whether an increase in capillary permeability induced by LPS in the absence of living bacteria also produces increased 67 Ga-labeled SSL localization, 2 mg LPS was inoculated in the left lung.…”

Mechanisms of Action and Clinical Application of Macrolides as Immunomodulatory Medications

“…TLR2 recognizes peptidoglycan and bacterial lipoproteins, and TLR4 and TLR5 recognize LPS and flagellin, respectively. LPS can promote mucus secretion through TLR4, even in neutropenic animals (287). Epithelial TLR signaling stimulated by LPS or flagellin is decreased by macrolides, and this appears to be mediated through the MAPK-NF-B pathway (255,257).…”

Expression of matrix metalloproteinases in pigs with hyperoxia-induced acute lung injury

“…To evaluate the severity of pulmonary oedema, the lung wet-to-dry weight ratio was determined [17]. A part of the lower lobe of the left lung was removed, and its wet weight was determined.…”