CARBOXYTERMINAL PEPTIDES WITH THE DIMERIC FORM OF PF4 RETAIN THE INHIBITORY EFFECT ON THE GROWTH OF HUMAN MEGAKARYOBLASTIC CELL-LINES

We have previously shown that platelet factor 4 (PF4) and beta-thrombo globulin (beta-TG) inhibit the growth of the human erythroleukemia cel l line (HEL). We further studied the effect of PF4, beta-TG, and vario us related peptides on human leukemic lineages to determine the specif icity and the relationship between the inhibitory activity and the mol ecular structure of PF4. The results showed that PF4 and beta-TG had a n inhibitory activity on the megakaryocytic growth, Furthermore, pepti des corresponding to the 1-24 and 13-24 residues but not to the 16-24 residue of the PF4 C-terminal region, the 21-29 and 20-28 C-terminal r egion of beta-TG and IL-8, inhibited only the megakaryocytic cell grow th. Interestingly, when Gin and Asn located at positions 15 and 24, re spectively, of the PF4 C-terminal region were replaced by Glu and Asp (C13-24DE), an increase in the inhibitory activity was observed. Moreo ver, the 13-24 monomeric form (13-24M) and modified form (13-24A), whe re a cysteine in C-terminal position 19 was substituted by arginine, w ere no longer active. These results suggest that the inhibitory activi ty of PF4 and its related peptides might be localized in their 13-24 C -terminal region and that a dimeric structure seems to be necessary to exert inhibitory activity.