The association of supernumerary microtubules and immotile cilia syndrome and defective neutrophil chemotaxis.

Abstract

Several ciliary defects are associated with poor motility or immotility of respiratory cilia. The defects include abnormalities in the axonemal structures or in the basal apparatus (1). Patients suffering from immotile cilia syndrome (ICS) show a heterogeneous clinical disease in which respiratory symptoms (viz. bronchiectasis, chronic bronchitis, otitis media) related to the ciliary dysfunction may be associated with other pathological conditions (i.e. situs viscerum inversus and male infertility). Even if numerous studies in humans and in experimental animals provide more information to explain, a t molecular level, the association between ICS and the above mentioned pathological states, to date, the association between ICS and a defective neutrophil chemotaxis is still object of debate (2). This report deals with four unrelated female patients (aged from 7 to 20 years) suffering from ICS in which a peculiar defect in ciliary configuration was found to be associated with a defective neutrophil chemotaxis. ICS was diagnosed by studying the mucociliary clearance and by examining the ultrastructural morphology of nasal cilia. Nasal mucociliary clearance time was tested by the saccharin method, measuring the time between placing saccharin (1 mm diameter particle) on the inferior turbinate and the moment when the subject tasted its sweetness on swallowing (3). Neutrophil chemotaxis was assessed, in symptom-free periods, “in vivo” and “in vitro” according to Senn (4) and Wilkinson ( 5 ) , respectively. In all patients immunological data were normal, whereas “in vivo” (36.1-17.6-15.9-16.1 x 10’ cells/cm2/24 h; normal values 68+ 10) and “in vitro” (chemotactic index: 121-123-119-1 13; normal values 145+ 11) neutrophil chemotaxis was impaired. The saccharin test (two or more different evaluations for each subject) was abnormal in all patients. In particular the clearance time (reference values 8-30 min) was >60 min in 3 patients, and about 50 min in one of the patients (50-52-55 min). The ultrastructural examination of respiratory cilia showed in all patients the presence of additional solitary peripheral microtubules outside or inside the 9+2 complex (Fig. 1). Cilia with axonemal supernumerary microtubules are reported to be associated to a ciliary dyskinesia (actually those cilia are classified as type V dyskinetic cilia) (1). Although data reported by several authors showed that an impairment of neutrophil chemotaxis is not a constant feature in ICS, the data presented here strongly suggest that a defective neutrophil