Effects of ethanol on in vitro ciliary motility.

Consumption of ethanol can impair lung function and slow total lung clearance. High concentrations of ethanol have been shown to slow or arrest ciliary beating. This study examined the effects of concentrations of alcohol comparable to blood levels achieved from social drinking on ciliary beat frequency. We obtained ciliated cells by brushing the trachea of unanesthetized sheep during fiber-optic bronchoscopy. The cells were suspended in a perfusion chamber and physiological conditions were maintained in vitro. Ciliary beat frequency and synchrony were determined by slow-motion analysis of video images obtained by interference contrast microscopy. Metachronal ciliary coordination was observed in all preparations. The ciliary beat frequency was stimulated at ethanol concentrations from 0.01 up to but not including 0.1%, unchanged at 0.5 and 1%, and slowed at 2%. While confirming inhibition of ciliary motility at very high ethanol levels, we observed no acute impairment of ciliary function at ethanol concentrations comparable to those achieved from social drinking. Indeed, we found an unexpected stimulation of ciliary beating at low levels of ethanol. How this alteration in ciliary beating would affect pulmonary clearance remains unknown at this time.

Effect of cyclic AMP on human blood platelets: induction of pseudopod formation and protein phosphorylation.

A variety of techniques, including immunofluorescence, electron microscopy and biochemical analysis, were used to examine shape changes and cytoskeletal reorganization of human blood platelets during treatment with N6,O2-dibutyryl adenosine 3',5'-cyclic monophosphoric acid (dbcAMP), and agent known to elevate the intracellular level of cyclic AMP (cAMP). Cytochemical analysis shows that the unstimulated platelets have a discoid shape with no obvious membrane projections. Platelets treated with dbcAMP produce pseudopod-like structures containing cytoskeletal proteins such as actin and microtubules. Biochemical analysis reveals that a 125,000 dalton phosphoprotein (P-125) is preferentially recruited into cytoskeletal fractions of platelets treated with dbcAMP. This protein, which is one of the substrates for cAMP-dependent kinase(s) and/or is closely associated with the cytoskeleton, may play an important role in regulating the shape changes and cytoskeletal reorganization that occur during the early stages of platelet activation.

Role of ciliary motility in acute allergic mucociliary dysfunction.

The purpose of this investigation was to determine if abnormal ciliary function contributes to allergic mucociliary dysfunction. In conscious sheep with Ascaris suum hypersensitivity, ciliated cells were obtained with a cytology brush and tracheal mucous velocity (TMV) was determined before and serially for 2 h following antigen inhalation. The recovered cells (also containing mast cells) were suspended in a chamber, and ciliary activity was viewed microscopically and recorded on videotape for subsequent slow-motion analysis of ciliary beat frequency (CBF). One hour after A. suum challenge mean CBF (+/- SE) showed a slight increase from a base-line value of 630 +/- 16 to 716 +/- 30 beats/min (P less than 0.05) when mean TMV was decreased to 57% of base line (P less than 0.05). After 2 h, both mean CBF and TMV returned toward base line. Since possible in vivo actions of chemical mediators liberated by antigen challenge may have been lost after suspension of the brushed cells, we also assessed the effects of antigen on CBF in vitro. A. suum caused a dose-dependent increase in CBF that was blocked by cromolyn sodium. We conclude that 1) allergic mucociliary dysfunction is not caused by a decrease in CBF and 2) antigen-induced release of chemical mediators increases CBF.

Sulfur dioxide induced airway hyperreactivity in allergic sheep.

The effects of a four-hour exposure (via a Plexiglas hood) to sulfur dioxide (SO2) on airway reactivity was studied in both normal and allergic conscious sheep. Allergic sheep were defined as animals in whom inhalation of Ascaris suum extract resulted in an increase in mean pulmonary flow resistance (RL). Airway reactivity (delta RL) was assessed by measuring the increase in RL after 18 breaths of 0.25% carbachol, from an initial value obtained after 18 breaths of buffered saline. RL and delta RL were determined prior to, immediately after and 24 hours following SO2 exposure in three groups of sheep: six normal sheep exposed to 5 ppm SO2 (group A); six normal sheep exposed to 10 ppm SO2 (group B) and seven allergic sheep exposed to 5 ppm SO2 (group C). RL was not affected by SO2 exposure in any group but both groups B and C showed increases in delta RL 24 hours after exposure. Since the increase in delta RL was greater in group C than in either groups A or B, we conclude that allergic sheep have enhanced susceptibility to the injurious airway effects of SO2.