E. Franzini et al., INHIBITION OF HUMAN NEUTROPHIL BINDING TO HYDROGEN PEROXIDE-TREATED ENDOTHELIAL-CELLS BY CAMP AND HYDROXYL RADICAL SCAVENGERS, Free radical biology & medicine, 21(1), 1996, pp. 15-23
Hydrogen peroxide (H2O2) increases adherence of human polymorphonuclea
r neutrophils (PMN) to cultured human umbilical vein endothelial cells
(HUVEC). Catalase and HO. scavengers did not affect the increased PMN
adherence to HUVEC stimulated by other compounds such as phorbol myri
state acetate (PMA) and thrombin, showing that the observed effect was
H2O2- and HO.-specific. This effect was inhibited by hydroxyl radical
s (HO.) scavengers and not by iron-chelators that do not penetrate the
cells, suggesting the involvement of intracellular HO. in the increas
ed adherence mechanism. An increase in cAMP inhibited H2O2-induced adh
erence, as observed with isoproterenol, isobutylmethylxanthine, and di
butyryl-cAMP. Similarly, pentoxifylline (Ptx), an HO. scavenger that a
lso increases cAMP, inhibited H2O2-mediated adherence but had no effec
t on that induced by PMA or thrombin. PKA inhibitors cancelled the Ptx
-induced inhibition-of H2O2-mediated adherence. However, PKA inhibitor
s or atrial natriuretic peptide that decreases cAMP did not increase a
dherence, showing that decrease in cAMP is not responsible for increas
ed adherence. HO. scavengers did not alter the H2O2-induced reduction
in cAMP levels, but did inhibit the effect of H2O2 on adherence. are c
onclude that HO. mediates the H2O2-induced increased in PMN adherence
to HUVEC, and that the increase in cAMP that mediates PKA activation d
ownregulates this effect.