GLUCAGON MODULATES SUPEROXIDE GENERATION IN HUMAN POLYMORPHONUCLEAR LEUKOCYTES

It has been found that leucocytes posses receptor sites for glucagon a nd glucagon was shown to increase during bacterial infection. To verif y the interconnection between glucagon, leucocytes and bacterial infec tion we studied the effect of glucagon on superoxide generation and se cond messenger transduction in PMNs. We found that glucagon could not stimulate chemiluminescence by itself but it could enhance FMLP- but n ot PMA-induced chemiluminescence in a concentration (50-800 pg/ml) dep endent manner. However, after incubation of PMNs With 10 muM of ST-638 (a tyrosine kinase inhibitor) the enhancement effect converted into i nhibitory effect. We also found that glucagon treatment of PMNs increa sed both IP3 and cyclic AMP levels as second messengers. ST-638 greatl y attenuated the IP3 increment in the glucagon-treated FMLP-stimulated PMNs. From these results we can conclude that glucagon could enhance superoxide generation from FMLP-stimulated PMNs by elevating IP3. Inhi bition of IP3 increment by tyrosine kinase blockade uncover the inhibi tory effect of the increasing cyclic AMP on superoxide production.