The role of vasoactive intestinal peptide (VIP) in megakaryocyte proliferation.
Megakaryocytopoiesis is a multistage process that involves differentiation of hematopoietic stem cells through the myeloid lineage, ultimately producing megakaryocytes and platelets. Vasoactive intestinal peptide (VIP) stimulates adenylate cyclase and induces differentiation in multiple cell types; VIP is expressed in hematopoietic stem cells and in megakaryocytes, but its function in these cells has not yet been delineated. The present study was designed to investigate whether the type 1 VIP receptor, VPAC1, mediates VIP effects on megakaryocytopoiesis. The human megakaryoblastic leukemia cell line (CMK) was transfected with VPAC1 and the transgene expression was confirmed by qualitative polymerase chain reaction and immunohistochemistry. The rate of proliferation and the patterns of differentiation were then compared for CMK and CMK/VPAC1 through multiple growth cycles. Upregulation of VPAC1 expression resulted in a decreased proliferation rate (p = 0.0003) and enhanced differentiation with CMK/VPAC1 cells having twice the cell surface area of control CMK cells (p = 0.001), thus increasing potential for proplatelet formation. These results suggest that VIP acts in an autocrine fashion via VPAC1 to inhibit megakaryocyte proliferation and induce proplatelet formation.
Nam
Chaneun
C
Department of Pediatrics, Division of Hematology/Oncology, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242, USA.
Case
Adam J
AJ
Hostager
Bruce S
BS
O'Dorisio
M Sue
MS
D019898:Autocrine Communication / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D045744:Cell Line, Tumor; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D007947:Leukemia, Megakaryoblastic, Acute; D008533:Megakaryocytes / Q000166:cytology* / Q000502:physiology*; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D015854:Up-Regulation / Q000502:physiology; D014660:Vasoactive Intestinal Peptide / Q000235:genetics / Q000378:metabolism*
D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D014660:Vasoactive Intestinal Peptide