Selective inflammatory response induced by intratracheal and intravenous administration of poly-L-arginine in guinea pig lungs.
Major basic protein (MBP) is a cationic protein found in eosinophil granules that was postulated to participate in the pathogenesis of bronchial asthma. Recently, it has been demonstrated that MBP level in serum or bronchoalveolar lavage (BAL) fluid was correlated with bronchial hyperresponsiveness (BHR) in asthmatics. A number a studies have established that MBP actions could be mimicked by synthetic polycations as poly-L-arginine. In this study, we investigated the effects of intratracheal and intravenous administration of poly-L-arginine on lung inflammatory response development. The intratracheal injection of poly-L-arginine at the doses of 1, 10, 100 nmol/animal increased the number of eosinophils (up to 3.2 fold) and neutrophils (up to 12 fold) in BAL fluid. Eosinophil and neutrophil infiltration was reversed by 88% and 67% respectively following low molecular weight heparin treatment (500 microg/animal). The intravenous injection of increasing doses of poly-L-arginine (1, 10, 100, 500 nmol/animal) increased the number of eosinophils (up to 2.7 fold) but not neutrophil infiltration in guinea pig lungs. Eosinophil infiltration was reversed by 87% following low molecular weight heparin treatment (1.5 mg/animal). Intratracheal treatment with poly-L-arginine (100 nmol/animal) produced an important increase of beta-glucuronidase, histamine, eosinophil peroxidase (EPO) and albumin levels in BAL fluid, whereas the intravenous treatment (500 nmol/animal) did not. These results show that the route of administration of poly-L-arginine greatly influences its effect on inflammatory cell recruitment since both administration routes elicited eosinophil migration but only the intratracheal route stimulated the migration of neutrophils. Moreover, poly-L-arginine appeared to induce other inflammatory responses since it increased beta-glucuronidase, histamine, EPO and albumin levels in BAL fluid following intratracheal treatment. These results also showed that low molecular weight heparin significantly blocks the inflammatory responses elicited by poly-L-arginine.
Institut de Pharmacologie de Sherbrooke, Faculté de Medecine, Université de Sherbrooke, PQ Canada.
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Arseneault
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Maghni
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Sirois
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D006168:Guinea Pigs; D007249:Inflammation / Q000209:etiology / Q000276:immunology / Q000473:pathology; D007275:Injections, Intravenous; D007442:Intubation, Intratracheal; D008168:Lung / Q000201:enzymology / Q000276:immunology / Q000473:pathology*; D010455:Peptides / Q000008:administration & dosage*; D011650:Pulmonary Alveoli / Q000378:metabolism
D010455:Peptides; C015462:polyarginine