Abstract
Elevation of cyclic (c) AMP levels in neutrophils (PMN) has been shown to inhibit cell adherence, but the mechanism of this inhibition has not been established. Since CR3 (Mac-1, Mo-1) is known to be essential for normal PMN adherence, and its expression is rapidly upregulated when PMN are activated, we tested the hypothesis that cAMP might act by blocking CR3 expression. Peripheral blood PMNs were incubated at 37° with the phosphodiesterase inhibitor, isobutyl methylxanthine (IBMX; 3x10−4M), followed by dibutyryl (db-) or 8-bromo (8Br-) cAMP (10−3M). Cells were then stimulated with n-formyl-methionyl-leucyl-phenylalanine (fMLP; 10−8M) or zymosan-activated serum (ZAS; 1:100). Upregulation of surface CR3 was quantitated using monoclonal antibodies and flow cytometry, and adherence was measured as % PMNs retained by nylon wool. IBMX and dbcAMP together, but not individually, inhibited the increase in CR3 expression (stim./resting ratio) induced by fMLP from 3.98±0.32 to 2.15±0.2 (p <0.01) and by ZAS from 2.56±0.09 to 1.94±0.07 (p <0.01). IBMX + dbcAMP, but neither alone, similarly inhibited PMN adherence induced by fMLP from 33.8±2.1% to 8.2±1.9% (p <0.001), and by ZAS from 25.3±2.5% to 15.6±0.7% (p <0.01). 8BrcAMP gave results similar to dbcAMP. Isobutanol, isobutyric acid, and diluent controls had no effect. Results for CR1 expression paralleled those for CR3. These studies suggest that elevating cAMP inhibits upregulation of surface CR1 and CR3 in PMNs. The decrease in surface CR3 may be responsible for the diminished PMN adherence caused by cAMP.
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Tosi, M., Berger, M. CYCLIC AMP INHIBITS NEUTROPHIL ADHERENCE BY BLOCKING SURFACE EXPRESSION OF THE CELL ADHESION MOLECULE, CR3. Pediatr Res 21 (Suppl 4), 319 (1987). https://doi.org/10.1203/00006450-198704010-00911
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DOI: https://doi.org/10.1203/00006450-198704010-00911