Adenosine and 2-phenylaminoadenosine (CV-1808) inhibit human neutrophil bactericidal function.
Adenosine is a natural autocoid and immunomodulator that serves an anti-inflammatory role. Stimulation of polymorphonuclear neutrophils (PMN) with soluble stimuli has been shown to inhibit the PMN oxidative burst. We examined the effects of adenosine and the adenosine analog 2-phenylaminoadenosine (CV-1808) on PMN bactericidal function. Adenosine (10 mM) and CV-1808 (10 to 100 microM) inhibited PMN killing of Staphylococcus aureus. There were more surviving bacteria after 240 min of incubation of PMN with S. aureus and adenosine (10 mM) or CV-1808 (100 microM) (254% +/- 45% and 739% +/- 88% of control, respectively) (P less than 0.05) than there were in the control. In contrast, inosine (10 mM), the major degradation product of adenosine, did not affect killing. Adenosine and CV-1808 did not alter cell association of S. aureus, but S. aureus-activated PMN superoxide release was decreased by adenosine (10 microM) and CV-1808 (10 microM) to 67% +/- 7% and 32% +/- 12% that of the control, respectively (P less than 0.05). Since adenosine inhibited PMN bactericidal function only at approximately 10,000 times peak physiological concentrations, endogenous adenosine levels would not be expected to adversely affect PMN bactericidal function. On the other hand, pharmacological concentrations of adenosine derivatives may decrease the oxidative burst and killing sufficiently to increase host susceptibility to infection.
Hardart
G E
GE
Department of Medicine, University of Virginia, Charlottesville 22908.
Sullivan
G W
GW
Carper
H T
HT
Mandell
G L
GL
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015169:Colony Count, Microbial; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D013211:Staphylococcus aureus / Q000276:immunology*; D013481:Superoxides / Q000378:metabolism
D013481:Superoxides; D006861:Hydrogen Peroxide; C026708:2-phenylaminoadenosine; D000241:Adenosine; D010100:Oxygen