ABSTRACT
Leukotriene B4(LTB4), derived from arachidonic acid, is a potent chemotactic agent and activating factor for hematopoietic cells. In addition to host defense in vivo, several eicosanoids have been reported to be involved in stem cell differentiation or proliferation. In this study, we investigated the effect of LTB4 on human cord blood CD34+ hematopoietic stem cells (HSCs). LTB4 was shown to induce proliferation of HSC and exert anti-apoptotic effect on the stem cells. Blockade of interaction between LTB4 and its receptor enhanced self-renewal of the stem cells. Effect of LTB4 on differentiation of CD34+ HSCs were confirmed by clonogenic assays, and induction of the expression of BLT2 (the low- affinity LTB4 receptor), during the ex vivo expansion was confirmed by reverse transcription-PCR. Our results suggest that LTB4-BLT2 interaction is involved in the cytokine-induced differentiation and ex vivo expansion of hematopoietic stem cells.
Subject(s)
Humans , Antigens, CD34/metabolism , Apoptosis/drug effects , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Fetal Blood/cytology , Hematopoietic Stem Cells/drug effects , Leukotriene B4/pharmacology , Receptors, Leukotriene B4/genetics , Reverse Transcriptase Polymerase Chain Reaction , Signal TransductionABSTRACT
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 formylmethion-ylleucylphenylalanine (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.