TY - JOUR
T1 - Cl- channels are expressed in human normal monocytes
T2 - A functional role in migration, adhesion and volume change
AU - Kim, M. J.
AU - Cheng, G.
AU - Agrawal, Devendra K.
PY - 2004/12
Y1 - 2004/12
N2 - Increased adhesion and diapedesis of monocytes appear to be primary initiating factors in the pathophysiology of occlusive vascular diseases, including atherosclerosis and restenosis. However, the underlying mechanisms of transendothelial migration and invasion of monocytes into the blood vessels are not known. Alterations in ion channels on the cell membrane are generally involved in induced changes in shape and volume. In the present study, we investigated the expression and functional role of chloride channels in freshly isolated human blood monocytes. The Cl- currents in whole-cells were measured by the patch-clamp technique. We observed whole cell Cl- currents, which were time-independent and outwardly rectifying. The chloride channel blockers 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) and R(+)-[(6,7-dichloro-2-cyclopentyl-2,3-dihydro-2-methyl-1-oxo-1H-inden-5yl)-oxy] acetic acid 94 (IAA94) attenuated the Cl- currents. NPPB and IAA94 also inhibited chemotaxis of monocytes, as measured in Boyden chemotactic chambers, with the same sensitivity. NPPB but not IAA94, increased the cell volume as measured by shape change, and decreased tumour necrosis factor (TNF)-α-induced monocyte adhesion to endothelial cells. These results suggest that monocytes contain Cl- channels which regulate transendothelial migration of monocytes, due presumably to an alteration in cell volume.
AB - Increased adhesion and diapedesis of monocytes appear to be primary initiating factors in the pathophysiology of occlusive vascular diseases, including atherosclerosis and restenosis. However, the underlying mechanisms of transendothelial migration and invasion of monocytes into the blood vessels are not known. Alterations in ion channels on the cell membrane are generally involved in induced changes in shape and volume. In the present study, we investigated the expression and functional role of chloride channels in freshly isolated human blood monocytes. The Cl- currents in whole-cells were measured by the patch-clamp technique. We observed whole cell Cl- currents, which were time-independent and outwardly rectifying. The chloride channel blockers 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) and R(+)-[(6,7-dichloro-2-cyclopentyl-2,3-dihydro-2-methyl-1-oxo-1H-inden-5yl)-oxy] acetic acid 94 (IAA94) attenuated the Cl- currents. NPPB and IAA94 also inhibited chemotaxis of monocytes, as measured in Boyden chemotactic chambers, with the same sensitivity. NPPB but not IAA94, increased the cell volume as measured by shape change, and decreased tumour necrosis factor (TNF)-α-induced monocyte adhesion to endothelial cells. These results suggest that monocytes contain Cl- channels which regulate transendothelial migration of monocytes, due presumably to an alteration in cell volume.
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U2 - 10.1111/j.1365-2249.2004.02635.x
DO - 10.1111/j.1365-2249.2004.02635.x
M3 - Article
C2 - 15544622
AN - SCOPUS:9644275230
SN - 0009-9104
VL - 138
SP - 453
EP - 459
JO - Clinical and Experimental Immunology
JF - Clinical and Experimental Immunology
IS - 3
ER -