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Impaired migration in vitro of neutrophils from patients with paroxysmal nocturnal haemoglobinuria.

Pedersen, TL; Yong, K; Pedersen, JO; Hansen, NE; Danø, K; Plesner, T; (1996) Impaired migration in vitro of neutrophils from patients with paroxysmal nocturnal haemoglobinuria. Br J Haematol , 95 (1) pp. 45-51.

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Abstract

Migration of neutrophils in patients with paroxysmal nocturnal haemoglobinuria (PNH) was studied using two different complement-free in vitro model systems, subagarose and transendothelial migration. In the subagarose migration assay the mean migration distance of PNH neutrophils was slightly, but significantly, reduced to 1236 microns (range 753-1586, n = 6) compared to a normal mean of 1476 microns (range 1076-1768, n = 6, P = 0.016). By immunocytochemical staining for the urokinase type plasminogen activator receptor (uPAR) which is a glycosyl-phosphatidyl-inositol (GPI) anchored protein expressed by normal, but not by PNH-affected, neutrophils, it was shown that the uPAR-positive subpopulation of normal neutrophils predominated among the faster migrating cells (60-80% normal cells at the front of migration) while uPAR-negative (i.e. PNH-affected neutrophils) were more numerous close to the application well (5-30% normal cells). When migration of neutrophils was tested across a monolayer of human umbilical vein endothelial cells (HUVEC) cultured on polycarbonate filters, there was a 3-4-fold impairment of the migration of the PNH-affected neutrophils both in the absence of stimulation and after stimulation with fMLP (P < 0.001 in both cases). After IL-1 stimulation of the endothelium the impairment was even more pronounced (8-fold difference, P < 0.001). When the endothelial cells were grown on collagen-coated filters the impairment of the migration of PNH neutrophils was less pronounced, but still significant after stimulation with fMLP and IL-1 (2-fold, P < 0.05 in both cases). These results demonstrate that there is a complement-independent impairment of migration of neutrophils from patients with PNH which may be related to their failure to express GPI-linked proteins involved in cell migration and/or adhesion such as the uPA receptor and the CD66b antigen.

Type: Article
Title: Impaired migration in vitro of neutrophils from patients with paroxysmal nocturnal haemoglobinuria.
Location: England
Keywords: Cell Movement, Hemoglobinuria, Paroxysmal, Humans, Immunohistochemistry, N-Formylmethionine Leucyl-Phenylalanine, Neutrophils, Plasminogen Activators, Receptors, Cell Surface, Receptors, Urokinase Plasminogen Activator
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: http://discovery.ucl.ac.uk/id/eprint/83934
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