Mechanisms of decrease in cytoplasmic motility of alveolar macrophages during immediate asthmatic response in dogs

Abstract

To study the cytoplasmic motility (CM) of alveolar macrophages (AM) during immediate asthmatic response, we measured remanent filed strength (RFS) in dogs in vivo after Ascaris suum-antigen (AA) inhalation. Four days after instillation of ferrimagnetic particles (Fe3O4, 3 mg/kg) into the right lower lobe bronchus, RFS was measured at the body surface immediately after magnetization of the Fe3O4 particles by an externally applied magnetic field. RFS decreased with time because of particle rotation (relaxation). Relaxation is thought to be correlated to CM of AM (J. Appl. Physiol. 55: 1196-1202, 1983). AA inhalation increased respiratory resistance (Rrs) in 10 dogs (responders; P less than 0.01), and did not change Rrs in five dogs (nonresponders; P greater than 0.50). The relaxation rate (lambda 0) significantly decreased because of AA inhalation in responders (P less than 0.01), whereas lambda 0 did not change in nonresponders (P greater than 0.50). Intravenous injection of indomethacin or diclofenac sodium (5 mg/kg) 30 min before AA inhalation completely inhibited the decrease in lambda 0 induced by AA inhalation, although both drugs did not inhibit the increase in Rrs (P greater than 0.10). In in vitro experiments, AM (5 x 10(6) cells) cells) harvested by bronchoalveolar lavage showed a significant dose-dependent decrease in lambda 0 with prostaglandins (PG) E1 and E2. However, histamine and platelet-activating factor increased lambda 0 significantly (P less than 0.01), whereas PGD2, PGF2 alpha, PGI2, thromboxane A2, leukotrienes B4, C4, and D4, and AA itself were without effect (P greater than 0.50). Furthermore, PGE2 aerosols mimicked AA-induced effects on AM.(ABSTRACT TRUNCATED AT 250 WORDS)