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The Journal of Immunology, Vol 154, Issue 5 2291-2302, Copyright © 1995 by American Association of Immunologists
ARTICLES |
E Crockett-Torabi, B Sulenbarger, CW Smith and JC Fantone
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109.
The effect of selective cell activation through L-selectin and Mac-1 molecules cross-linking on neutrophil superoxide anion (O2-) generation and changes in intracellular calcium [Ca2+]i was investigated. Cross- linking of L-selectin using different mAbs induced a rapid and transient increase in [Ca2+]i and O2- generation by neutrophils that were dependent on the extent of L-selectin cross-linking and mAb epitope binding. In addition, cross-linking of L-selectin induced an up- regulation of surface Mac-1 expression on neutrophils. Cross-linking of Mac-1 molecules with mAb also induced significant changes in [Ca2+]i levels and O2- generation by neutrophils, which was also dependent on the epitope binding by mAb. Pretreatment of neutrophils with LPS caused a marked decrease in the expression of L-selectin molecules and significant inhibition (i.e., 59 +/- 4%) of anti-L-selectin mAb- dependent O2- generation and [Ca2+]i signal. In contrast, LPS pretreatment caused a significant up-regulation of Mac-1 molecules on neutrophil and enhanced O2- generation by neutrophils. The data indicate that cross-linking of L-selectin and Mac-1 initiates changes in [Ca2+]i and O2- production in neutrophils and suggest that these distinct adhesion molecules independently may play important regulatory roles in modulating neutrophil-endothelial cell interactions, transmigration, and neutrophil function at sites of tissue injury.
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