Effects of inhaled PAF in humans on circulating and bronchoalveolar lavage fluid neutrophils. Relationship to bronchoconstriction and changes in airway responsiveness.
We have compared the effect of 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 lavage (BAL) 4 h later. The mean density and volume of circulating neutrophils were measured by metrizamide gradients and flow cytometry, respectively. PAF caused a decrease in Vp20 of 38.2 +/- 4.5% at 5 min after the first inhalation (p less than 0.001). This was associated with a fall in the peripheral blood neutrophil count from 3.15 +/- 0.3 to 1.1 +/- 0.3 x 10(6) per ml (p less than 0.001), followed by a rebound neutrophilia (p less than 0.01). The mean density of peripheral blood neutrophils fell significantly at 15 min (p less than 0.02), with a return to baseline values despite further PAF inhalations; this was associated with an increase in neutrophil volume (n = 4; p less than 0.05). The numbers of neutrophils (x 10(5] 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 less than 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 less than 0.02) 3 days after PAF. Inhaled lyso-PAF was inactive in all these respects.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Allergy and Clinical Immunology, National Heart & Lung Institute, London, England.
A J
AJ
Wardlaw
K F
KF
Chung
R
R
Moqbel
A J
AJ
MacDonald
A
A
Hartnell
M
M
McCusker
J V
JV
Collins
P J
PJ
Barnes
A B
AB
Kay
D000280:Administration, Inhalation; D001980:Bronchi / Q000187:drug effects* / Q000502:physiology; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D006801:Humans; D007958:Leukocyte Count / Q000187:drug effects; D016210:Methacholine Chloride; D008688:Methacholine Compounds; D009504:Neutrophils / Q000187:drug effects*; D010972:Platelet Activating Factor / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*
D008688:Methacholine Compounds; C029271:O-deacetyl platelet activating factor; D010972:Platelet Activating Factor; D016210:Methacholine Chloride