| Abstrakt: |
Human neutrophils possess a superoxide (O)-forming NADPH oxidase which is activated by the chemoattractants, N-formyl- l-methionyl- l-leucyl- l,-phenylalanine (fMet-Leu-Phe), complement C5a, platelet-activating factor and leukotriene B. We studied the roles of cAMP and cGMP in the regulation of Oformation using the cell-permeant analogues of cyclic nucleotides, N,2′- O-dibutyryl adenosine 3′:5′-cyclic monophosphate (BtcAMP) and N,2′- O-dibutyryl guanosine 3′:5′-cyclic monophosphate (BtcGMP). BtcAMP inhibited Oformation induced by these chemoattractants to similar extents. BtcGMP as low as 10 μmol/l significantly inhibited Oformation induced by fMet-Leu-Phe at a submaximally effective concentration (50 nmol/1), and BtcGMP was more effective in diminishing Oformation than BtcAMP. In contrast, BtcGMP did not affect Oformation induced by fMet-Leu-Phe at a maximally effective concentration (1 μmol/l). BtcGMP (0.1 and 1 mmol/l) enhanced Oformation induced by 0.1 μmol/l C5a by 23% and 49%, respectively, and BtcGMP antagonized inhibition of Oformation caused by BtcAMP. BtcGMP inhibited platelet-activating factor-induced Oformation to a lesser extent than BtcAMP and had no effect on that induced by leukotriene B. BtcAMP and BtcGMP had no effect on Oformation induced by NaF, γ-hexachlorocyclohexane, phorbol myristate acetate, A 23187 and arachidonic acid. Our data suggest that: 1. BtcAMP generally inhibits chemoattractant-stimulated Oformation. 2. BtcGMP inhibits fMet-Leu-Phe- and platelet-activating factor-stimulated Oformation but potentiates C5a-induced Oformation. 3. The lack of effect of cyclic nucleotides on Oformation induced by agents other than receptor agonists indicates that cAMP and cGMP modulate early steps of the signal transduction processes initiated by chemoattractants. [ABSTRACT FROM AUTHOR] |
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