Identification and characterization of neutrophil chemotactic activity in aspirin-induced asthma.
In order to determine if mast cell mediators are released during aspirin challenge in aspirin-sensitive asthmatics, we measured neutrophil chemotactic activity, which has been shown to be an indicator of mast cell degranulation. Four aspirin-sensitive asthmatic subjects were given doses of aspirin (60 to 325 mg) previously determined to cause a 20 to 30% fall in forced expiratory volume in one second (FEV1); pulmonary function was followed by serial spirograms and body plethysmography. Serum was obtained before and at 30, 60, 90, 120, 180, and 240 min after challenge, corresponding to the times of pulmonary function measurements. Neutrophil chemotactic activity was measured using a modified Boyden chamber assay. Maximal bronchoconstriction occurred 60 to 120 min after aspirin ingestion. An increase in neutrophil chemotactic activity of 300 to 600% over baseline was detected in all subjects. In 3 subjects, neutrophil chemotactic activity release paralleled bronchoconstriction, and in 1 subject, it followed onset of bronchoconstriction. Physicochemical analysis showed that the neutrophil chemotactic activity eluted in the void volume of a Sephadex G-200 column (greater than or equal to 250,000 daltons) and from Sephadex QAE anion exchange chromatography in a region corresponding to 0.2 to 0.3 M NaCl. Its isoelectric point was in the pH range 6.5 to 7.5. These characteristics are compatible with neutrophil chemotactic factor of mast cell origin. Pretreatment with sodium cromolyn (40 mg) completely eliminated neutrophil chemotactic factor release, but only partially suppressed the fall in FEV1 in 2 subjects and had no effect on FEV1 fall in a third.(ABSTRACT TRUNCATED AT 250 WORDS)
D000328:Adult; D000368:Aged; D001241:Aspirin / Q000009:adverse effects*; D001249:Asthma / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology*; D002630:Chemotactic Factors / Q000097:blood*; D002634:Chemotaxis, Leukocyte; D002850:Chromatography, Gel; D002852:Chromatography, Ion Exchange; D004205:Cromolyn Sodium / Q000494:pharmacology; D003594:Cytoplasmic Granules / Q000502:physiology; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D016209:Interleukin-8; D007525:Isoelectric Focusing; D008297:Male; D008407:Mast Cells / Q000502:physiology; D008875:Middle Aged; D009504:Neutrophils / Q000502:physiology
D002630:Chemotactic Factors; D016209:Interleukin-8; D004205:Cromolyn Sodium; D001241:Aspirin