Retroviral transformation of cerebral microvascular endothelial cells:
macrophage-like and microvascular endothelial cell properties
DH Robinson, MK Warren, LT Liang, JJ Oprandy, TB Nielsen and YH Kang
Diving Medicine Department, Naval Medical Research Institute, Bethesda, MD
20814-5055.
We report that L-cell-conditioned medium (LCM) transforms porcine cerebral
microvascular (PCMV) endothelial cells into cells with macrophage-like
properties. LCM is known to contain both cytokine(s) and the L-cell virus,
a murine retrovirus found in the L929 cell and LCM. Our evidence suggests
that both LCM cytokine(s) and the L-cell virus are involved in this PCMV
endothelial cell transformation. Criteria for transformation include focus
formation, decreased serum requirements for growth, changes in morphology
including nonadherence, propagation in suspension culture, and a decreased
growth response to stimulation with a known endothelial cell mitogen.
Macrophage-like characteristics of this transformed cell, designated as
RVTE, include pinocytosis of low-density lipoprotein, Fc receptor-mediated
phagocytosis, phagocytosis of bacteria and zymosan, the expression of
macrophage enzyme markers, and constitutive production of colony-
stimulating factor 1. However, the transformed cell retains several
properties of the nontransformed cell including the expression of FVIII:RAg
and in vitro self-organization into capillary-like structures. Cloning of
RVTE cells clearly shows that both macrophage- like and cerebral
microvascular endothelial cell properties are present in the same cell.
During self-organization, nontransformed cells express morphologic and
functional characteristics classically associated with the macrophage.
These findings suggest that some brain capillary pathophysiologies could
involve macrophage-like cerebral microvascular endothelial cells.
Furthermore, the "reticuloendothelial" phenotypic repertoire expressed by
this transformed cerebral microvascular endothelial cell may show that the
cerebral capillary endothelial cell in vivo is derived from a hematopoietic
and/or phagocytic precursor.
Volume 77,
Issue 2,
pp. 294-305,
01/15/1991
Copyright © 1991 by The American Society of Hematology
