L-selectin Stimulation of Canine Neutrophil Initiates Calcium Signal Secondary to Tyrosine Kinase Activation

Neutrophils play an important role in myocardial ischemia-reperfusion injury. Neutrophil adhesion to the vascular endothelium is one of the important early mechanisms that lead 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. Cross-linking of canine neutrophil L-selectin using anti-L-selectin antibody induced a rapid and transient increase in intracellular Ca2+ levels and superoxide anion generation that were dependent on the extent of L-selectin cross-linking. 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.