The effects of interleukin-8 on neutrophil fMetLeuPhe receptors, CD11b expression and metabolic activity, in comparison and combination with other cytokines.
The effect of the chemotactic cytokine, IL-8, on neutrophil function was compared with that of of other cytokines, GM-CSF, G-CSF TNF alpha and IFN-gamma. IL-8 rapidly stimulated a three-fold enhancement of the fMLP-stimulated respiratory burst, but this priming effect was transient compared with the slower and sustained effects of GM-CSF and IFN gamma. Apart from G-CSF, IL-8 was the weakest priming agent and was weaker than GM-CSF in priming arachidonic acid metabolism stimulated by calcium ionophore. When incubated in combination, IL-8 and TNF alpha were highly synergistic in their effects on respiratory burst priming, whereas IL-8 and GM-CSF showed little synergy. In contrast, IL-8 was as potent as GM-CSF at increasing the expression of neutrophil chemotactic peptide receptors and the beta 2 integrin, CD11b. The latter was maximally upregulated within 5 min of stimulation with IL-8, whereas the effect of GM-CSF was much slower. The kinetics of neutrophil respiratory burst priming by IL-8 were the same when measured in whole blood samples and in purified cell suspensions, and IL-8 dose-response curves were similar, showing that the low affinity IL-8 receptors on erythrocytes do not rapidly sequester circulating IL-8. The data suggest that IL-8 plays a minor role in priming neutrophil function and that a more major activity is the regulation of neutrophil adhesion and migration.
Roberts
P J
PJ
Department of Haematology, University College London Medical School.
Pizzey
A R
AR
Khwaja
A
A
Carver
J E
JE
Mire-Sluis
A R
AR
Linch
D C
DC
D015703:Antigens, CD / Q000032:analysis / Q000187:drug effects*; D016718:Arachidonic Acid / Q000097:blood; D018845:CD11 Antigens; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D006801:Humans; D016209:Interleukin-8 / Q000494:pharmacology* / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000187:drug effects* / Q000378:metabolism; D018000:Receptors, Peptide / Q000187:drug effects* / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism
D015703:Antigens, CD; D018845:CD11 Antigens; D016207:Cytokines; D016209:Interleukin-8; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D013481:Superoxides; D016718:Arachidonic Acid