Adenosine regulates the respiratory burst of cytokine-triggered human neutrophils adherent to biologic surfaces.
The effect of adenosine on the respiratory burst was investigated using human neutrophils adherent to serum-coated surfaces. Adenosine caused complete suppression of the respiratory burst elicited by TNF-alpha, FMLP, or CSF for granulocytes; partial suppression of the response to CSF for granulocytes/macrophages, Staphylococcus aureus, Escherichia coli, Listeria monocytogenes, or uncoated polystyrene surfaces; and no suppression of the response to PMA. In most experiments, 4.7 x 10(-7) M and 2.5 x 10(-8) M adenosine caused 50% suppression of H2O2 release in response to TNF-alpha and FMLP, respectively, and 10 microM caused 100% suppression. Preexposure of neutrophils to ADP blocked the inhibitory effect of adenosine. With adherent neutrophils, there is a prolonged lag period in the onset of the respiratory burst in response to cytokines. Adenosine was fully suppressive if its addition was delayed past the first third of this lag period, or if it was removed during the last third of the lag period. A 10-min pulse with adenosine was most inhibitory when delivered in the middle third of the lag period. Dihydrocytochalasin B abolished the suppressive effect of adenosine on H2O2 release in response to FMLP. Thus adenosine, at concentrations found in human plasma, is a potent but selective inhibitor of the respiratory burst of adherent human neutrophils in response to physiologic, soluble stimuli, and ADP is a potentially physiologic counter-suppressant. Adenosine appears to exert most of its effect during a discrete interval within the lag period before onset of the respiratory burst, and may affect the coupling of agonist receptors to the cytoskeleton.
de la Harpe
J
J
Beatrice and Samuel A. Seaver Laboratory, Cornell University Medical College, New York 10021.
Nathan
C F
CF
D015762:2-Chloroadenosine; D000241:Adenosine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D000244:Adenosine Diphosphate / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002449:Cell Aggregation / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000037:antagonists & inhibitors / Q000502:physiology; D007700:Kinetics; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology*; D010101:Oxygen Consumption / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D015762:2-Chloroadenosine; D009240:N-Formylmethionine Leucyl-Phenylalanine; D000244:Adenosine Diphosphate; D000241:Adenosine