Multiple signalling pathways in the C5a-induced expression of adhesion receptor Mac-1.
The CD11/CD18 family of leukocyte glycoproteins is essential in the process of adherence to endothelial and other cells that occurs during the acute inflammatory response. The cell surface expression of one member of this family, CD11b/CD18, or Mac-1, is increased on monocytes, neutrophils and other cell types by a number of agents, including chemotactic peptides and lipid mediators. The intracellular signalling mechanisms which control Mac-1 expression are not fully understood. In this report we have investigated the role of G proteins and extracellular Ca2+ in the stimulation of Mac-1 upregulation by the chemoattractant C5a in the human monocyte-like cell line, U937. Two signal transduction pathways are apparently involved and can be distinguished by their sensitivity to pertussis toxin, which inhibits activation of the Gi class of G proteins. The results indicate that a pertussis toxin-insensitive influx of extracellular Ca2+ may be one part of a network of signals leading to Mac-1 upregulation on U937 cells. This is in contrast to the stimulation of this process in neutrophils by chemotactic peptide, which is reported to be entirely dependent on pertussis toxin sensitive G proteins and independent of extracellular Ca2+.
Monk
P N
PN
Department of Molecular Biology and Biotechnology, University of Sheffield, UK.
Barker
M D
MD
Partridge
L J
LJ
D000199:Actins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D015936:Complement C5a / Q000378:metabolism / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D016177:Macrophage-1 Antigen / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects; D037342:Pertussis Toxin; D010703:Phorbol Esters / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000199:Actins; D016177:Macrophage-1 Antigen; D010703:Phorbol Esters; D017382:Reactive Oxygen Species; D010566:Virulence Factors, Bordetella; D015936:Complement C5a; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D002118:Calcium