Role of lysophosphatidylcholine in eosinophil infiltration and resistance in airways.
1. Lysophosphatidylcholine (Lyso-PC), which is synthesized by phospholipase A2, is generally considered to induce adhesion molecules. However, little is known about the involvement of Lyso-PC in the pathogenesis of bronchial asthma. The present study was designed to examine whether pre-exposure to Lyso-PC causes eosinophil recruitment and an increase in resistance in airways. 2. Eosinophils in bronchoalveolar lavage fluid (BALF) and the airway walls were enumerated after inhalation of 0.5 mg/mL Lyso-PC to guinea-pigs for 10 min. Respiratory resistance (Rrs) was recorded continuously over 6 h after inhalation of an equi-dose of Lyso-PC for an equivalent period. 3. The proportion of eosinophils was increased from 10.7 +/- 3.3 to 27.5 +/- 3.1% (P < 0.0001) in BALF 6 h after inhalation of Lyso-PC, whereas the proportion of neutrophils and lymphocytes was not increased. Histological examination also showed uniform distribution of eosinophils in the airway wall of bronchi and bronchioles 6 h after inhalation of Lyso-PC. The number of eosinophils (/10 h.p.f.) in the bronchi and bronchioles was increased from 43.5 +/- 16.8 to 154.8 +/- 21.7 (P < 0.0001) and from 34.8 +/- 0.7 to 106.0 +/- 26.6 (P < 0.01), respectively. This eosinophil infiltration was similarly observed 24 h later. 4. Next, we examined the effects of eosinophil infiltration induced by Lyso-PC on Rrs. Inhalation of Lyso-PC caused a slow increase in Rrs and the percentage increase in Rrs was 19.8 +/- 1.9% (P < 0.0001) 6 h later. Eosinophil infiltration and an increase in Rrs did not occur after inhalation of physiological saline. These phenomena induced by Lyso-PC were diminished by pretreatment with dexamethasone (6 micro g/kg per day for 3 days). 5. Lysophosphatidylcholine causes eosinophil infiltration and a subsequent increase in resistance in airways. Our results indicate that Lyso-PC may be involved in the pathophysiology of bronchial asthma.
Second Department of Internal Medicine, School of Medicine, Nagoya University, Nagoya, Japan.
Osamu
O
Nishiyama
Hiroaki
H
Kume
Masashi
M
Kondo
Yasushi
Y
Ito
Masafumi
M
Ito
Kenichi
K
Yamaki
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002452:Cell Count; D004804:Eosinophils / Q000276:immunology / Q000473:pathology*; D006168:Guinea Pigs; D008168:Lung / Q000473:pathology; D008214:Lymphocytes / Q000473:pathology; D008244:Lysophosphatidylcholines / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D009504:Neutrophils / Q000473:pathology; D051381:Rats; D013997:Time Factors
D008244:Lysophosphatidylcholines