The effect of the platelet-derived glycosaminoglycan serglycin on in vitro proplatelet-like process formation.
The formation of proplatelet-like processes on megakaryocytes cultured in vitro has been shown to be inhibited by prothrombin, found residually in human serum, which is converted in culture to thrombin. This study reports that another factor found in human serum will counter this inhibition and permit proplatelet-like process formation to occur in vitro even in the presence of inhibitory concentrations of thrombin. The factor was purified from human platelet lysates and identified by amino acid sequence analysis as the proteoglycan serglycin. A similar, if not identical, factor was found at elevated levels in the plasma of thrombocytopenic rabbits. Serglycin probably functions as a proplatelet potentiator by virtue of a tendency to complex with thrombin. Thrombin in complex with serglycin retains its enzymatic properties, but is apparently sterically hindered from interacting with the megakaryocyte cell surface. In preliminary studies, the in vivo administration of serglycin in mice resulted in an increased number of circulating platelets when given in combination with interleukin-6 (IL-6).
Hunt
P
P
Laboratory of Stem Cell Biology, Amgen Corporation, Amgen Center, Thousand Oaks, CA 91320.
Hokom
M M
MM
Hornkohl
A
A
Wiemann
B
B
Rohde
M F
MF
Arakawa
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001792:Blood Platelets / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D002809:Chondroitin Sulfates / Q000494:pharmacology; D004359:Drug Therapy, Combination; D006168:Guinea Pigs; D006410:Hematopoiesis / Q000187:drug effects; D015850:Interleukin-6 / Q000494:pharmacology; D008533:Megakaryocytes / Q000166:cytology; D008969:Molecular Sequence Data; D011509:Proteoglycans / Q000032:analysis / Q000494:pharmacology*; D011516:Prothrombin / Q000032:analysis; D011817:Rabbits; D013917:Thrombin / Q000494:pharmacology; D013921:Thrombocytopenia / Q000097:blood; D033921:Vesicular Transport Proteins
D015850:Interleukin-6; D011509:Proteoglycans; D033921:Vesicular Transport Proteins; C075430:serglycin; D011516:Prothrombin; D002809:Chondroitin Sulfates; D013917:Thrombin