EFFECT OF HEPARIN AND A LOW-MOLECULAR-WEIGHT HEPARINOID ON PAF-INDUCED AIRWAY RESPONSES IN NEONATALLY IMMUNIZED RABBITS

1 We have investigated the effect of an unfractionated heparin prepara tion, a low-molecular weight heparinoid (Org 10172) and the polyanioni c molecule polyglutamic acid against PAF-induced airway hyperresponsiv eness and pulmonary cell infiltration in neonatally immunized rabbits in vivo. 2 Exposure of neonatally immunized rabbits to aerosolized pla telet activating factor(PAF) (80 mug ml-1 for 60 min) elicited an incr ease in airway responsiveness to inhaled histamine 24 h and 72 h follo wing challenge which was associated with an infiltration of inflammato ry cells into the airways, as assessed by bronchoalveolar lavage (BAL) . 3 A significant increase in the total numbers of cells recovered fro m BAL fluid was associated with significantly increased cell numbers o f neutrophils, eosinophils and mononuclear cells 24 h following PAF ex posure. The numbers of eosinophils and neutrophils in the airways rema ined elevated 72 h after challenge. 4 The intravenous administation of an unfractionated preparation of heparin (100 units kg-1) or Org 101 72 (I 00 mug kg-1) 30 min prior to PAF exposure significantly inhibite d the airway hyperresponsiveness induced by PAF, 24 h and 72 h followi ng challenge. PAF-induced hyperresponsiveness was not significantly af fected by prior intravenous administration of polyglutamic acid (100 m ug kg-1). 5 The intravenous administration of unfractionated heparin ( 100 units kg-1), Org 10172 (100 mug kg-1) or polyglutamic acid (100 mu g kg-1) 30 min prior to PAF exposure significantly inhibited the expec ted increase in total cell infiltration. 6 This study shows that unfra ctionated heparin and a low-molecular weight heparinoid, Org 10172, ar e capable of inhibiting both the airway hyperresponsiveness and pulmon ary cell infiltration induced by PAF in the rabbit.