Plasma Ceramides and Sphingomyelins of Pediatric Patients Increase in Primary Ciliary Dyskinesia but Decrease in Cystic Fibrosis.

We investigated plasma sphingomyelin (CerPCho) and ceramide (Cer) levels in pediatric patients with cystic fibrosis (CF) and primary ciliary dyskinesia (PCD). Plasma samples were obtained from CF (n = 19) and PCD (n = 7) patients at exacerbation, discharge, and stable periods. Healthy children (n = 17) of similar age served as control. Levels of 16-24 CerPCho and 16-24 Cer were measured by LC-MS/MS. Concentrations of all CerPCho and Cer species measured at exacerbation were significantly lower in patients with CF than PCD. 16, 18, 24 CerPCho, and 22, 24 Cer in exacerbation; 18, 24 CerPCho, and 18, 20, 22, 24 Cer at discharge; 18, 24 CerPCho and 24 Cer at stable period were significantly lower in CF patients than healthy children (p < 0.001 and p < 0.05). All CerPCho and Cer levels of PCD patients were significantly higher except 24 CerPCho and 24 Cer during exacerbation, 24 CerPCho at discharge, and 18, 22 CerPCho levels at stable period (p < 0.001 and p < 0.05) compared with healthy children. There was no significant difference among exacerbation, discharge, and stable periods in each group for Cer and CerPCho levels. This is the first study measuring plasma Cer and CerPCho levels in PCD and third study in CF patients. The dramatic difference in plasma levels of most CerPCho and Cer species found between two diseases suggest that cilia pathology in PCD and CFTR mutation in CF seem to alter sphingolipid metabolism possibly in opposite directions.

Membrane fluidity of polymorphonuclear leukocytes from children with primary ciliary dyskinesia.

Plasma membrane fluidity and heterogeneity of polymorphonuclear leukocytes (PMN) were investigated in seven children with primary ciliary dyskinesia (PCD) and 17 healthy controls. Membrane fluidity and heterogeneity were studied by measuring the steady state fluorescence anisotropy and fluorescence decay of 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH) incorporated into PMN plasma membrane. Our results show an increase in membrane fluidity at the surface level of PMN from patients with PCD. Distribution analysis of TMA-DPH lifetime values indicate an increase in membrane heterogeneity in subjects with PCD. The observed changes in the physicochemical properties of the membrane could lead to alterations in the function of PMN from children with PCD.

Assessment of neutrophil function in dogs with primary ciliary dyskinesia.

Compared with neutrophils from healthy dogs, neutrophils from 2 dogs with primary ciliary dyskinesia had increased distance of random migration, but fewer of the neutrophils migrated. The affected dogs had an increase in the numbers of Staphylococcus aureus phagocytized. Lymphocyte blastogenesis in the affected dogs in response to standard mitogens was considered to be normal.

Leukocyte locomotory function in children with the immotile cilia syndrome.

The random motility of polymorphonuclear leucocytes (PMN), cellular chemotaxis and chemokinesis in kinetic fashion in 4 patients with immotile cilia syndrome (ICS) have been evaluated. No impairment of granulocyte ability of orientation and migration was found. Ultrastructural alterations of cilia which are the primary factor in the pathogenesis of respiratory tract disease in patients with ICS do not impair the PMN function.

[Are there mucoviscidosis specific humoral factors? 1: Properties, prevalence, preparation, formation]. / Gibt es mukoviszidosespezifische humorale Faktoren? Teil 1: Eigenschaften, Vorkommen, Präparation, Bildung.

In 1967 Spock et al. reported on the serum of cystic fibrosis (CF) homozygotes containing a factor altering the coordination of ciliary motion in rabbit tracheal explants. Just in 1967 Mangos et al. found sweat and saliva from CF homozygotes having an inhibitory effect on sodium reabsorption in the rat parotid gland. Since that time the existence of CF specific humoral factors was supposed. Hitherto mainly biological tests (especially tests of ciliary dyskinesia) were used to prove these factors. These tests caused different results which even were doubtful with regard to the existence of CF specific proteins. Recently it is possible to differentiate between proteins with effects of ciliary dyskinesia and a CF specific protein by means of high sensitive biochemical and immunological methods of protein distinction. In future one can expect elucidation of question related to the importance of CF protein in pathogenesis and diagnosis of cystic fibrosis.

Defective neutrophil motility in patients with primary ciliary dyskinesia.

Microtubules are important in the regulation of the motile functions of a variety of cells, including leukocytes, ciliated cells and spermatozoa. Polymorphonuclear leukocyte function was studied in ten patients with primary ciliary dyskinesia, an inherited disorder of microtubules in sperm tails and cilia. Neutrophil chemotaxis in Boyden chambers was slightly reduced, but only one patient showed a migration below normal values. In vivo mobilization of polymorphonuclear leukocytes into skin windows was also slightly decreased. In contrast, neutrophil polarization and orientation was normal. The bactericidal activity of neutrophils from patients with primary ciliary dyskinesia was normal, while the ingestion of bacteria was decreased. The abnormalities of neutrophil function in patients with primary ciliary dyskinesia are related to motility. It is suggested that the microtubule defect responsible for the abnormal pattern of ciliary beating is a general abnormality also responsible for the depression of polymorphonuclear leukocyte motility.