Permeabilization and calcium-dependent activation of rabbit polymorphonuclear leukocytes by poly-L-arginine

Abstract

In the absence of extracellular Ca²⁺, poly-l-arginine induces little lysozyme release from rabbit polymorphonuclear leukocytes (PMNs), The polycation causes plasma membrane damage, which is evident from the release of the cytoplasmic enzyme lactate dehydrogenase (LDH). In the presence of Ca²⁺ concentrations higher than 0.2 mM, poly-l-arginine induces a strong lysozyme release that is superimposed on the membrane-damaging effect. The results suggest that poly-L-arginine permeabilizes the plasma membrane, enabling Ca²⁺ to enter the cell, which results in the exocytotic release of granule constituents. The GTP analog GTP_γS shifts the Ca²⁺ requirement of exocytosis to slightly higher concentrations, whereas it completely inhibits poly-l-arginine-induced LDH release. Pertussis toxin gives a moderate inhibition, and La³⁺ completely inhibits poly-L-arginine-induced enzyme release. Whereas poly-l-arginine alone induces little superoxide generation in rabbit PMNs, there is a synergistic enhancement of superoxide production when GTP_γS and poly-l-arginine are present together. Guanine nucleotides apparently have a modulating effect on the actions of poly-l-arginine on the PMN, but the nature of this effect remains to be determined.