Chemotaxis of Blood Neutrophils from Patients with Primary Ciliary Dyskinesia

Abstract

Primary ciliary dyskinesia is characterized by chronic upper and lower respiratory infections which are caused by the grossly impaired ciliary transport. Since the cilia and neutrophils both utilize microtubular system for their movement, it has been speculated that neutrophil motility such as chemotaxis might be impaired in patients with primary ciliary dyskinesia. Neutrophils were purified from whole blood from 16 patients with primary ciliary dyskinesia and from 15 healthy controls. Chemotactic responses of neutrophils to leukotriene B4 (LTB4), complement 5a (C5a), and formylmethionylleucylphenylalanine (fMLP) were examined using the under agarose method. The chemotactic differentials in response to LTB4, C5a, and fMLP in neutrophils from the patient group were significantly lower than the corresponding values in neutrophils from the control group (p<0.05 for all comparisons). The difference in chemotactic index between the two groups was statistically significant for LTB4 and fMLP (p<0.05 for both comparisons), but not for C5a (p=0.20). Neutrophils from patients with primary ciliary dyskinesia showed a decreased chemotactic response as compared with those from normal subjects. It is concluded that the increased frequency of respiratory tract infection in patients with primary ciliary dyskinesia is possibly due to the defective directional migration of neutrophils, as well as to the defective mucociliary clearance of the airways.

Neutrophils from Patients with Primary Ciliary Dyskinesia Display Reduced Chemotaxis to CXCR2 Ligands

“…The directionality of migration was comparable for control and PCD PMN (data not shown). The decreased chemotactic response was, however, not associated with defective spontaneous migration, because the mean accumulated distance in response to buffer stimulation was similar for control and PCD PMN, confirming published findings ( 7 ).…”

“…Our study of the chemotactic response of PCD neutrophils to four chemoattractants, C5a, LTB4, and the chemokines CXCL5 and CXCL8, can be motivated by multiple arguments. First, there is no consensus whether PCD neutrophils are affected in their migratory response, because both normal ( 8 , 9 ) and decreased ( 6 , 7 ) migration of PCD neutrophils has been reported in the past. Of note, chemokines were not included in those studies.…”

“…The pulmonary damage in PCD might also be aggravated by abnormal functioning neutrophilic granulocytes. Indeed, in some old reports, the migratory capacity of peripheral blood neutrophils from patients with PCD (PCD PMN) toward N -formylmethionyl-leucyl-phenylalanine (fMLP), leukotriene B4 (LTB4) and complement component 5a (C5a) has been shown to be reduced ( 6 , 7 ), whereas others reported unaffected chemotaxis of PCD PMN to the bacterial peptide fMLP or rather aspecific stimuli, such as zymosan ( 8 , 9 ).…”

Kartagener syndrome – a very rare cause of neonatal respiratory distress

“…Because of impaired mucociliary clearance, infants with PCD have a major risk of recurrent, chronic infections of the lungs, middle ear and paranasal sinuses. Also, male infertility and defects in neutrophil chemotaxis can be present (5). Ciliated epithelium covers most areas of the upper and lower respiratory tract, reproductive organs and ependyma.…”

Studying Electrotaxis in Microfluidic Devices

“…Different chemical and physical stimuli have been identified and reported as important factors to cause cell migration, phenomena named “-taxis”. Chemotaxis, characterizing how cells move under stimulus of specific chemical gradients, is shown to be crucial in human diseases [ 13 ] such as inflammation [ 14 , 15 ], Acquired Immune Deficiency Syndrome (AIDS) [ 16 ] and Primary Ciliary Dyskinesia (PCD) [ 17 ]. Roussos et al reviewed in detail how chemotaxis affects various behaviors of tumor cells and stromal cells in vivo [ 18 ].…”