Activation of human neutrophils through L-selectin and Mac-1 molecules.
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.
Crockett-Torabi
E
E
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109.
Sulenbarger
B
B
Smith
C W
CW
Fantone
J C
JC
D000818:Animals; D000911:Antibodies, Monoclonal; D002118:Calcium / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002465:Cell Movement; D003432:Cross-Linking Reagents; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D066298:In Vitro Techniques; D019041:L-Selectin; D008070:Lipopolysaccharides / Q000494:pharmacology; D016177:Macrophage-1 Antigen / Q000502:physiology*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D003432:Cross-Linking Reagents; D007136:Immunoglobulins; D008070:Lipopolysaccharides; D016177:Macrophage-1 Antigen; D013481:Superoxides; D019041:L-Selectin; D002118:Calcium