Effect of erythromycin on endotoxin-induced microvascular leakage in the rat trachea and lungs.
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.
Tamaoki
J
J
First Department of Medicine, Tokyo Women's Medical College, Japan.
Tagaya
E
E
Yamawaki
I
I
Sakai
N
N
Nagai
A
A
Konno
K
K
D000667:Ampicillin / Q000494:pharmacology; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D002433:Cefaclor / Q000494:pharmacology; D004396:Coloring Agents; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000494:pharmacology*; D004917:Erythromycin / Q000494:pharmacology*; D007211:Indoles; D008168:Lung / Q000033:anatomy & histology / Q000098:blood supply*; D008297:Male; D008833:Microcirculation / Q000503:physiopathology; D009504:Neutrophils / Q000166:cytology; D009929:Organ Size; D009942:Organometallic Compounds; D051381:Rats; D017207:Rats, Sprague-Dawley; D014132:Trachea / Q000098:blood supply* / Q000166:cytology
D004396:Coloring Agents; D004731:Endotoxins; D007211:Indoles; D009942:Organometallic Compounds; C015445:copper phthalocyanine; D004917:Erythromycin; D002433:Cefaclor; D000667:Ampicillin