Membrane Fluidity of Polymorphonuclear Leukocytes from Children with Primary Ciliary Dyskinesia

Abstract

ABSTRACT. 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-(Ctrimethylammoniumphenyl)d-phenyl-1,3 J-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. (Pediarr Res 34: 725-728, 1993) Abbreviations PMN, polymorphonuclear leukocyte PCD, primary ciliary dyskinesia TMA-DPH, 144-trimethy1ammoniumphenyl)-6-phenyl-1,3,5-hexatriene FMLP, N-formyl-methionyl-leucyl-phenylalanine r,, steady state fluorescence anisotropy PMA, phorbol myristate acetate PMN from subjects with PCD can have an abnormal locomotory system. Defects in orientation (l,2), migration (1-3) and chemotaxis (3-5) have been reported. All these activities are the result of complex events mediated by the plasma membrane and cytoskeleton of PMN. Specific and dynamic interactions of plasma membrane components are essential for an adequate membrane function (6). Membrane fluidity has an important role in modulating cell functions, affecting the conformation of membrane proteins and the exposure and diffusion of membrane components. Fluidity is a complex physicochemical feature that depends upon mobility and order of membrane constituents (6, 7). Changes in composition and molecular organization are the principal determinants of alterations of membrane fluidity observed in many human diseases (8,9).In this study, we have evaluated plasma membrane fluidity of PMN obtained from children with PCD by measuring r, and fluorescence decay of a probe incorporated into the plasma membranes. As a fluorescent probe, we have used TMA-DPH, which is incorporated at the lipid-water interface region bilayer.

Primary Ciliary Dyskinesia: Longitudinal Study of Lung Disease by Ultrastructure Defect and Genotype

“…Conceivably, CCDC39 and CCDC40 may have a role in other nonepithelial cells that affect lung health. Early studies showed that neutrophils extracted from some individuals with PCD may have defective motility causing impaired chemotaxis and bacterial killing (35,36). Because these studies were performed before the advent of genetic testing, it is unclear whether the neutrophil phenotype is related to specific PCD genotypes.…”

Chemotaxis of Blood Neutrophils from Patients with Primary Ciliary Dyskinesia

“…A variety of abnormalities in the microtubule structure and arrangement in cilia and sperm tails have now been described in patients with primary ciliary dyskinesia (18). While attempts to define microtubule structural abnormalities in patient' s neutrophils that are similar to those seen in cilia and sperm tails have been unsuccessful (7), a functional study of neutrophils from the patients has shown that an integrated cytoplasmic microtubule-membrane interaction is essential for their motility (19).…”

Ccdc103 promotes myeloid cell proliferation and migration independent of motile cilia

“…Primary neutrophils isolated from PCD patients have impaired directed migration to chemokines in in vitro assays ( Afzelius et al, 1980 ; Walter et al, 1990 ; Kantar et al, 1993 ; Cockx et al, 2017 ). Furthermore, microtubule destabilization via nocodazole treatment decreases the ability of neutrophils to migrate appropriately toward a chemical stimulus ( Gundersen and Bulinski, 1988 ; Kadir et al, 2011 ; Yoo et al, 2012 ).…”