Abstract
Glycosaminoglycanpolysulfate (GAGPS) was used to study effects on the production of superoxide anion (O-2) in human peripheral neutrophils. Superoxide generation in response to activating factor, N-formyl-methionyl-leucyl-phenylalanine (FMLP), phorbol 12-myristate 13-acetate (PMA) and PA68 (a seed extract) was inhibited by GAGPS and the quantitative analysis indicated that this effect was does-dependent. The concentration of cytosolic ionized calcium [Ca2+] i, was measured in intact neutrophils using a fluorescent indicator trapped in the cytoplasm. A given rise of [Ca2+] i elicited by FMLP was also inhibited by GAGPS, in a fashion similar to, that of the inhibition of O-2 generation in neutrophils. The results suggested that GAGPS induce both calcium-dependent FMLP and calciumindependent PMA response to inhibite [Ca2+] i released from neutrophils. These nonspecific effects, taken together with the increase in lactate dehydrogenase activity brought on by high concentrations of GAGPS, would appear to implicate GAGPS as having an important role in neutrophil cytotoxity. The results, thus, suggest that the actions of GAGPS are similar to those of superoxide dismutase (SOD), a scanvenger of O-2.
