Platelet activation releases megakaryocyte-synthesized apolipoprotein J, a highly abundant protein in atheromatous lesions.
Apolipoprotein J (apoJ) is an abundant glycoprotein in many biological fluids, and its constitutive high level synthesis is characteristic of many epithelial cells exposed to harsh fluids such as urine, bile, and gastric secretions. In addition, dramatic induction of apoJ occurs in cells surrounding several kinds of pathological lesions. Because platelets and circulating inflammatory cells represent critical elements in numerous pathological processes, we evaluated bone marrow cells for the presence of apoJ. Based upon messenger RNA in situ hybridization and immunofluorescent protein detection, high-level apoJ gene expression and protein accumulation occurred exclusively in mature megakaryocytes. Our results indicate that apoJ is stored in platelet granules and is released into extracellular fluid following platelet activation. Because atheromatous plaque development involves platelet aggregation and activation, we looked for and found abundant apoJ protein in advanced human atheromatous lesions. Thus, platelet sequestration and activation may lead to the rapid deployment of apoJ into sites of vascular injury. We hypothesize that platelet-derived apoJ participates in both short-term wound repair processes and chronic pathogenic processes at vascular interfaces.
Witte
D P
DP
Department of Pathology, Children's Hospital Medical Center, Cincinnati, OH 45229.
Aronow
B J
BJ
Stauderman
M L
ML
Stuart
W D
WD
Clay
M A
MA
Gruppo
R A
RA
Jenkins
S H
SH
Harmony
J A
JA
D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology; D001792:Blood Platelets / Q000378:metabolism / Q000648:ultrastructure; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D051152:Clusterin; D006023:Glycoproteins / Q000032:analysis / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008533:Megakaryocytes / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D016253:Microscopy, Immunoelectron; D018832:Molecular Chaperones; D015539:Platelet Activation / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis
C495242:CLU protein, human; C495243:Clu protein, mouse; D051152:Clusterin; D006023:Glycoproteins; D018832:Molecular Chaperones; D012333:RNA, Messenger