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 granule s that was postulated to participate in the pathogenesis of bronchial asthm a. Recently, it has been demonstrated that MBP level in serum or bronchoalv eolar lavage (BAL) fluid was correlated with bronchial hyperresponsiveness (BHR) in asthmatics. A number a studies have established that MBP actions c ould be mimicked by synthetic polycations as poly-L-arginine. In this study , we investigated the effects of intratracheal and intravenous administrati on of poly-L-arginine on lung inflammatory response development. The intrat racheal 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 t o 12 fold) in BAL fluid. Eosinophil and neutrophil infiltration was reverse d by 88% and 67% respectively following low molecular weight heparin treatm ent (500 mu g/animal). The intravenous injection of increasing doses of pol y-L-arginine (1, 10, 100, 500 nmol/animal) increased the number of eosinoph ils (up to 2.7 fold) but not neutrophil infiltration in guinea pig lungs. E osinophil infiltration was reversed by 87% following low molecular weight h eparin treatment (1.5 mg/animal). Intratracheal treatment with poly-L-argin ine (100 nmol/animal) produced an important increase of beta-glucuronidase, histamine, eosinophil peroxidase (EPO) and albumin levels in BAL fluid, wh ereas the intravenous treatment (500 nmol/animal) did not. These results sh ow that the route of administration of poly-L-arginine greatly influences i ts 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, histami ne, EPO and albumin levels in BAL fluid following intratracheal treatment. These results also showed that low molecular weight heparin significantly b locks the inflammatory responses elicited by poly-L-arginine.