Effects of Inhaled PAF in Humans on Circulating and Bronchoalveolar Lavage Fluid Neutrophils: Relationship to Bronchoconstriction and Changes in Airway Responsiveness

Abstract

We have compared the effect of the inhaled platelet activating factor (PAF) on circulating neutrophils with its ability to induce bronchoconstriction and bronchial hyperresponsiveness in humans. Human volunteers inhaled PAF, given as six successive inhalations 15 min apart, followed by bronchoalveolar (BAL) 4 h later. The mean density and volume of circulating neutrophils were measured by metrizamide gradients and flow cytometry, respectively. PAF caused a decreased in Vp30 of 38.2 .+-. 4.5% at 5 min after the first inhalation (p < 0.001). This was associated with a fall in the peripheral blood neutrophil count from 3.15 .+-. 0.3 to 1.1 .+-. 0.3 .times. 106 per ml (p < 0.001), followed by a rebound neutrophilia (p < 0.01). The mean density of peripheral blood neutrophils fell significantly at 15 min (p < 0.02), with a return to baseline values despite further PAF inhalations; this was associated with an increase in neutrophil volume (n = 4; p < 0.05). The numbers of neutrophils (.times. 105) in BAL fluid after PAF were significantly greater than after inhalation of lyso-PAF: 7.1 .+-. 1.4 (n = 7) versus 1.3 .+-. 0.3 (n = 5, p < 0.01); eosinophil counts did not change significantly. The PC40 (the concentration of methacholine needed to cause a fall in Vp30) decreased from 17.1 (GSEM 1.40) to 8.7 (1.44) mg/ml (n = 12, p < 0.02) 3 days after PAF. Inhaled lyso-PAF was inactive in all these respects. The degree of bronchoconstriction induced by PAF correlated positively with BAL neutrophil count (r = 0.93, p < 0.01), but the increase in PC40 correlated negatively with BAL neutrophil count (r = 0.83, p < 0.05). Our observations suggest that inhaled PAF causes activation of circulating neutrophils with subsequent infiltration into the airway and lung spaces; however, there is no evidence that these events are directly related to the development of PAF-induced hyperresponsiveness.