SRS‐A leukotrienes decrease the activity of human respiratory cilia

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Abstract
Summary: We have studied the effects of the slow reacting substance of anaphylaxis (SRS‐A) constituents leukotrienes (LT) C4 and D4 on the ciliary activity of human respiratory cells. The ciliary beat frequency on human nasal cells harvested by cell scraping from the inferior turbinate was measured in a blind design by a microphoto‐oscillographic technique. A total of 740 ciliated cells from seventy‐four cell scrapings were studied. Mean baseline of ciliary beat frequency was 10.2 Hz. The ciliary beat frequency exhibited a pronounced variability in the spontaneous changes between the cell scrapings, yet less so within cell samples from the cell scrapings. We, therefore, evaluated the effect of the test solutions relative to the spontaneous decrease found during simultaneous perfusion with control solution of samples from the same cell scrapings. LTC4, 3–300 nmol/l, caused a highly significantly dose‐related decrease in the ciliary beat frequency by up to approximately 20% as compared to the corresponding control solution. The effect of LTC4 was significantly inhibited by the SRS‐A receptor antagonist FPL 55712 (10μmol/l), but not by indomethacin (10 μmol/l). LTD4, 300 nmol/l, also decreased the ciliary beat frequency. LTB4, which is a leukotriene, although without the sulphidopeptide side chain of the SRS‐A leukotrienes, did not affect the ciliary beat frequency in a concentration of 100 nmol/l. This would seem to confirm the structure specificity of the elucidated effect of the SRS‐A leukotrienes. Histamine (100 μmol/l) did not affect the ciliary beat frequency. The present study demonstrates that the SRS‐A leukotrienes have a specific cilio‐depressive effect, which may contribute to mucus obstruction in the lower airways in asthma and other chronic airway diseases.