Occupancy of adenosine receptors on human neutrophils inhibits respiratory burst stimulated by ingestion of complement-coated particles and occupancy of chemoattractant but not Fc receptors.
Chemoattractants are generated at inflammatory loci that not only induce neutrophils (PMNs) to leave the vasculature but also stimulate PMNs to release potentially toxic agents (e.g., H2O2, O2- or OH). We have recently demonstrated that endothelium releases adenosine which, when bound to a specific receptor on the PMN surface, inhibits release of toxic oxygen metabolites from stimulated PMN. To determine whether occupancy of adenosine receptors modulates generation and release of oxygen metabolites, we have studied the effect of 2-chloroadenosine on O2- generation and O2 consumption in response to opsonized zymosan particles (STZ) and immune complexes (IC). 2-Chloroadenosine inhibits, in a dose-dependent fashion, O2- generation by neutrophils that have been exposed to C3b-coated particles (STZ). Inhibition of O2- generation is similar in the presence or absence of cytochalasin B (IC50 = 53 +/- 19 and 16 +/- 5 nM, respectively, P = NS). Since occupancy of adenosine receptors might inhibit only externalization but not generation of oxygen metabolites, we studied the effect of 2-chloroadenosine on oxygen consumption by activated neutrophils. 2-Chloroadenosine inhibited O2 consumption stimulated by STZ and the surrogate bacterial chemoattractant FMLP; however, inhibition of O2 consumption varied with the presence or absence of cytochalasin B. In contrast, when neutrophils were stimulated by immune complexes, 2-chloroadenosine only minimally inhibited O2- release and O2 consumption (10 +/- 5 and 5 +/- 4% inhibition, respectively). Thus, occupancy of adenosine receptors inhibits O2 consumption in parallel with inhibition of O2- release.(ABSTRACT TRUNCATED AT 250 WORDS)
Kubersky
S M
SM
Department of Medicine, New York University Medical Center, NY 10016.
Hirschhorn
R
R
Broekman
M J
MJ
Cronstein
B N
BN
D015762:2-Chloroadenosine / Q000494:pharmacology*; D000936:Antigen-Antibody Complex / Q000276:immunology; D003571:Cytochalasin B / Q000494:pharmacology; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000037:antagonists & inhibitors*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D011961:Receptors, Fc / Q000502:physiology*; D011983:Receptors, Purinergic / Q000187:drug effects* / Q000502:physiology; D015054:Zymosan / Q000037:antagonists & inhibitors
D000936:Antigen-Antibody Complex; D011961:Receptors, Fc; D011983:Receptors, Purinergic; D015762:2-Chloroadenosine; D003571:Cytochalasin B; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015054:Zymosan; D010100:Oxygen