Negative regulation of human megakaryocytopoiesis by human platelet factor 4 (PF4) and connective tissue-activating peptide (CTAP-III).

We have previously reported that human platelet factor 4 (PF4) and beta-thromboglobulin inhibit human megakaryocyte (meg) colony formation in vitro. Here, we report further findings concerning the effect of PF4 as well as another platelet-derived factor: connective tissue-activating peptide (CTAP-III). Addition of these factors (2.5-10 micrograms/ml) into normal marrow cultures resulted in a significant decrease of meg colonies, especially the mixed-meg colonies, BFU-meg and large CFU-meg, suggesting that they inhibit both proliferation and maturation of meg progenitor cells, with a predominant effect on earlier progenitor cells. Comparison of the effects of the two factors showed that their major effects were similar, with some difference in inhibitory degree. These results indicate that both PF4 and CTAP-III are potent inhibitors of meg colony formation and involved in negative autocrine regulation of megakaryocytopoiesis.