G. Fóris

Effect of elastin peptides on human monocytes: Ca2+ mobilization, stimulation of respiratory burst and enzyme secretion.

The effect of elastin peptides (Kappa-elastin) was investigated on human monocytes. The data presented here indicate that elastin peptides increase the intracellular Ca2+ level measured by Quin 2 fluorescence and mediate the release of beta glucuronidase and elastase. The O2 consumption and H2O2 release were stimulated in a dose-dependent manner. The early rise of cAMP was followed by a return to the original level at 30 min and by a concomitant increase of cGMP level. The action of elastin peptides on intracellular calcium level and cGMP levels may well be related to its previously demonstrated chemotactic activity. These activities may well play a role in the modifications of the extracellular matrix following elastin degradation as observed in atherosclerosis, emphysema and aging.

Immunology of elastin: study of anti-elastin peptide antibodies by DOT immunobinding assay

In order to further investigate the role of the immune system in the arteriosclerotic process, we investigated the anti-elastin peptide antibodies (AEAb) of the IgG and IgM types by DOT immunobinding assay in the sera of patients suffering from various arteriosclerotic diseases. In total 232 control and pathological sera were studied. In obliterative arteriosclerosis of the legs 90%, ischemic heart disease 67% and hypertension 60% of sera were positive for AEAb of the IgG type independent of age. In the case of diabetes mellitus, however, the duration of the disease was determinant. In rheumatoid arthritis, the results were negative. No clear-cut positivity could be demonstrated in stroke patients either. These results indicate that AEAb can be detected in some diseases and DOT appears to be an appropriate method for the AEAb screening in various diseases.

Effects of Elastin Peptides on Ion Fluxes

The degradation of elastin by elastase-type enzymes was shown to play an important role in several pathological processes such as the development of emphysema (Crystal, 1976; Bignonet al., 1978), arteriosclerosis (Robertet al., 1980, 1984), and a variety of skin diseases (Franceset al., 1984). All these enzymes, although of different natures (Bourdillonet al., 1984), are able to hydrolyze elastin and release soluble peptides. The released peptides (mainly kappa elastin, KE) were shown to have a variety of biological properties (Robertet al., 1970; Jacobet al., 1984). One of these was the chemotactic effect on monocyte and fibroblasts (Senioret al., 1980). Robertet al. (1967, 1970) demonstrated their antigenic nature. Rabbits immunized with elastin peptides were shown to develop severe arteriosclerosis (Robertet al., 1971; Jacobet al., 1984) and also lesions of pulmonary arteries. Transmembrane cation fluxes (Na+ , K+ , Ca2+ ) were shown to play an important role in cell activity regulation (Scullyet al., 1984; Blausteinet al., 1984). The chemotactic peptide receptors were shown to be coupled to the phosphoinositide-specific phospholipase C through a guanine nucleotide regulatory protein (Berridgeet al., 1984). This receptor activation involves hydrolysis of phosphoinositides followed by generation of inositol trisphosphate and diacylglycerol. The inositol trisphosphate is believed to induce the release of Ca2+ from an intracellular storage and as a consequence the level of intracellular free Ca2+ is increased (Reynolds, 1985). Furthermore, the formation of inositol tetrakisphosphate from inositol trisphosphate seems to have ionophore effects (Trimbleet al., 1987). Our aims were to investigate the effects of elastin peptides on ion fluxes and to elucidate their mechanism of action at the cellular and intracellular levels.