Jd. Belcher et al., Activated monocytes in sickle cell disease: potential role in the activation of vascular endothelium and vaso-occlusion, BLOOD, 96(7), 2000, pp. 2451-2459
Sickle cell anemia is characterized by painful vaso-occlusive crises. It is
hypothesized that monocytes are activated in sickle cell disease and can e
nhance vasoocclusion by activating endothelium. To test this hypothesis, hu
man umbilical vein endothelial cells (HUVEC) and human microvascular endoth
elial cells (MVEC) with sickle and normal mononuclear leukocytes were incub
ated, and endothelial activation was measured. Endothelial cells incubated
with sickle mononuclear leukocytes were more activated than those incubated
with normal mononuclear leukocytes, as judged by the increased endothelial
expression of adhesion molecules and tissue factor and the adhesion of pol
ymorphonuclear leukocytes (PMNL). Monocytes, not lymphocytes or platelets,
were the mononuclear cells responsible for activating endothelial cells. Si
ckle monocytes triggered endothelial nuclear factor-kappa B (NF-kappa B) nu
clear translocation, Cell-to-cell contact of monocytes and endothelium enha
nced, but was not required for, activation. Antibodies to tumor necrosis fa
ctor-alpha (TNF-alpha) and interleukin-1-beta (IL-1 beta) blocked activatio
n of the endothelium by monocytes, Peripheral blood monocytes from patients
with sickle cell disease had 34% more IL-1 beta (P = .002) and 139% more T
NF-alpha (P = .002) per cell than normal monocytes, Sixty percent of sickle
monocytes expressed the adhesion molecule ligand CD11b on their surfaces c
ompared with only 20% of normal monocytes (P = .002). Serum C-reactive prot
ein, a marker of systemic inflammation, was increased 12-fold in sickle ser
um than in normal serum (P = .003). These results demonstrate that sickle m
onocytes are activated and can, in turn, activate endothelial cells. It is
speculated that vascular inflammation, marked by activated monocytes and en
dothelium, plays a significant role in the pathophysiology of vasoocclusion
in sickle cell anemia. (Blood, 2000;96:2451-2459) (C) 2000 by The American
Society of Hematology.