Inhibition of lipopolysaccharide-induced pulmonary emphysema by intratracheally instilled recombinant secretory leukocyte proteinase inhibitor.
Experiments were performed to test whether recombinant secretory leukocyte proteinase inhibitor (rSLPI) was able to prevent the development of lipopolysaccharide (LPS)-mediated pulmonary emphysema, hemorrhage, and secretory cell metaplasia (SCM) in hamsters. Several groups of eight animals were intratracheally treated for four weeks, twice a week with 0.5 mg Escherichia coli LPS or with saline. In the first experiment, an additional group of eight hamsters was treated with 0.5 mg LPS mixed with 0.5 mg rSLPI, and the animals received another instillation of 0.5 mg rSLPI 7 h later. In the second experiment, 0.5 mg LPS, mixed with 1 mg rSLPI, was given while additional instillations of 1 mg rSLPI were performed 7 h and 31 h after the first dosage. In the third experiment, 0.5 mg LPS, mixed with 0.5, 1.5, or 3.0 mg rSLPI, was given while additional instillations of 0.5, 1.5, and 3.0 mg rSLPI, respectively, were performed 24 h and 48 h after the first dosage. Hamster lungs were examined for emphysema, hemorrhage, and SCM. In all three series of experiments, we observed a significant inhibition of LPS-mediated emphysema by rSLPI. This inhibition tended to be dose related. Inconclusive results were obtained on the inhibition of LPS-mediated hemorrhage. The development of LPS-mediated SCM was not affected by rSLPI. The LPS-mediated polymorphonuclear leukocyte (PMN) influx did not change when administrations of rSLPI were given additionally. We conclude that rSLPI is able to diminish significantly the development of LPS-mediated pulmonary emphysema in hamsters.(ABSTRACT TRUNCATED AT 250 WORDS)
Rudolphus
A
A
Department of Pulmonology, University Hospital, Leiden, The Netherlands.
Stolk
J
J
Dijkman
J H
JH
Kramps
J A
JA
D000818:Animals; D000906:Antibodies / Q000097:blood; D000918:Antibody Specificity; D006224:Cricetinae; D004353:Drug Evaluation, Preclinical; D004926:Escherichia coli; D006470:Hemorrhage / Q000188:drug therapy / Q000209:etiology / Q000276:immunology; D007322:Instillation, Drug; D008070:Lipopolysaccharides; D008168:Lung / Q000473:pathology; D008171:Lung Diseases / Q000188:drug therapy / Q000209:etiology / Q000276:immunology; D008647:Mesocricetus; D008679:Metaplasia / Q000188:drug therapy / Q000209:etiology / Q000276:immunology; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D011656:Pulmonary Emphysema / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage* / Q000276:immunology; D013997:Time Factors; D014132:Trachea
D000906:Antibodies; D008070:Lipopolysaccharides; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D011994:Recombinant Proteins; D015842:Serine Proteinase Inhibitors