L-selectin stimulation of canine neutrophil initiates calcium
signal secondary to tyrosine kinase activation.
Crockett-Torabi, Elahe, and Joseph C. Fantone.
Department of Pathology, The University of Michigan -Medical
School, Ann Arbor, Michigan 48109-0602
APStracts 3:0404H, 1996.
Neutrophils play an important role in myocardial ischemia-reperfusion
injury. Neutrophil adhesion to the vascular endothelium is one of the
important early mechanisms which leads to reperfusion injury. The
leukocyte adhesion molecule, L-selectin, plays a major role in the
initial interaction between neutrophils and endothelial cells.
Intervention aimed at blocking selectins or their associated ligands
can exert cardioprotective effects. The purpose of this study was to
examine the role of L-selectin in the initiation of transmembrane
signaling and regulation of canine neutrophil responses. Crosslinking
of canine neutrophils L-selectin using anti-L-selectin antibody
induced a rapid and transient increase in intracellular calcium
([Ca2+]i) levels and superoxide anion generation which were dependent
on the extent of L-selectin crosslinking. The responses were
significantly inhibited by the protein tyrosine kinase inhibitor,
genistein. The results demonstrate that ligation of canine neutrophil
L-selectin is coupled to intracellular signal transduction pathways
and the generation of second messengers which may independently play
important regulatory roles in modulating neutrophil-endothelial cell
interactions.
Received 4 March 1996; accepted in final form 10 September 1996.
APS Manuscript Number H204-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 7 October 1996