INFLAMMATORY RESPONSES INDUCED BY POLY-L-ARGININE IN RAT LUNGS IN-VIVO

The inflammatory responses induced by the synthetic polycation poly-L- arginine injected either into the pleural cavity or into the trachea i n rats have been investigated. Poly-L-arginine (4-40 nmol/rat) injecte d intrapleurally induced exudate formation and leucocyte migration (ma inly polymorphonuclear cells). The exudate formation (but not cell mig ration) was dependent on the molecular weight of the poly-L-arginine u sed (24 and 115 kD). The poly-L-arginine-induced pleurisy was mainly d ependent on activation of mast cells since it was significantly reduce d either in rats depleted of their stores of histamine and serotonin o r in rats previously treated with the serotonin receptor antagonist me thysergide. The polyanions heparin and dermatan sulphate when administ ered intrapleurally with the polycation markedly reduced the exudate f ormation. Poly-L-arginine (115 kD, 8.5 nmol/rat) injected intratrachea lly caused lung oedema, increased leucocyte number and protein content of bronchoalveolar lavage, respiratory insufficiency and 60% mortalit y in 6 h. Depletion of histamine and serotonin stores or of circulatin g neutrophils decreased the leucocytes in bronchoalveolar lavage but d id not increase survival rate, whereas the polyanion dermatan sulphate prevented the mortality completely. These results suggest that the in flammatory changes caused by poly-L-arginine are dependent on mast cel l activation but that the lethality after intratracheal administration is due to electrostatic interactions of the polycation with anionic s urfaces present in the pulmonary epithelium.