Effect of leukotriene D4 on ciliary activity in human, guinea-pig and rat respiratory mucosa.
Leukotriene D4 (LTD4) is a potent bronchoconstrictor and inflammatory mediator in asthma. Data concerning the effects of LTD4 on ciliary function in the respiratory tract are sparse and contradictory. The purpose of the present study was to clarify the effects of LTD4 on mucociliary activity using the tracheal mucosa of two laboratory animal species, guinea-pig and rat, as well as human nasal mucosa. The ciliary beat frequency (CBF) was measured photoelectrically and determined by Fast Fourier Transform computer analysis. Additionally the structure of ciliated epithelia of guinea-pig trachea after LTD4-immersion was investigated using a scanning electron microscope (SEM). In all tissues, LTD4 increased CBF showing a bell-shaped dose-response curve. The maximum effect was 75 +/- 30% in guinea-pig at 10(-9) mol/l, 119 +/- 49% in rat at 10(-7) mol/l, and 86 +/- 28% at 10(-6) mol/l in human tissue. In guinea-pig tracheal mucosa, there was an indication of an increase in the amount of mucus and disorientation of cilia were seen by SEM after immersion in LTD4. These findings suggest that LTD4 stimulates ciliary activity, but impairs the orientation of cilia.
Joki
S
S
Department of Pharmacology and Toxicology, University of Kuopio, Finland.
Saano
V
V
Koskela
T
T
Toskala
E
E
Bray
M A
MA
Nuutinen
J
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000818:Animals; D016085:Bronchoconstrictor Agents / Q000494:pharmacology*; D016022:Case-Control Studies; D004353:Drug Evaluation, Preclinical; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology*; D017998:Leukotriene D4 / Q000494:pharmacology*; D008297:Male; D008855:Microscopy, Electron, Scanning; D008875:Middle Aged; D009079:Mucociliary Clearance / Q000187:drug effects*; D009092:Mucous Membrane / Q000187:drug effects; D009297:Nasal Mucosa / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D014132:Trachea / Q000187:drug effects*
D016085:Bronchoconstrictor Agents; D018836:Inflammation Mediators; D017998:Leukotriene D4