Blood-platelets-damaging activity of some synthetic Streptococcus peptidoglycan subunits and analogues

A series of 25 synthetic subunits or analogues of streptococcal peptidoglycan was tested for their ability to damage rabbit blood platelets. The morphological changes of the platelets were studied on an ultrastructural level. Minimal subunit structure able to produce a complete lysis of the platelets was found to be muramyldipeptide (MDP). Comparable lysis of platelets was also caused by muramyltetrapeptide and MDP containing D-Ala instead of L-Ala. The lytic effect was dose-dependent and was exhibited rather after high doses of the substances used (up to 500 micrograms/ml). For the lytic reaction, the configuration of C3 and C4 in the muramyl residue of MDP was essential. Many substances produced only degranulation without lysis of the platelets and some of them did not influence the platelet ultrastructure at all. The paper presents some structure-to-function relationships of the compounds and shows that the platelet-damaging activity of peptidoglycan may be related to certain portions of the peptidoglycan molecule. This activity should be tested when the immunomodulatory substances derived from the bacterial peptidoglycan are searched for.