Integrin mediated adhesion of mononuclear cells from patients with familial hypercholesterolemia.
BACKGROUND
Low-density lipoproteins (LDL) can induce the adhesion of monocytes to endothelial cells. Monocytes of patients with familial hypercholesterolemia (FH) are exposed to high concentrations of LDL, and it has been reported that adhesiveness of these cells in hypercholesterolemic patients is enhanced. We investigated whether LFA-1 or VLA-4 mediated adhesion is altered in FH patients and whether HMG-CoA reductase inhibitors influence this adhesion.


METHODS
LFA-1 and VLA-4 mediated adhesion to ICAM-1 and VCAM-1 coated beads was investigated using freshly isolated monocytes and T-lymphocytes from patients with homozygous FH, heterozygous FH (before and after cholesterol lowering treatment), and from controls. In addition, the expression of beta1- and beta2-integrins on these cells was determined.


RESULTS
Both LFA-1 and VLA-4 mediated adhesion and integrin expression of monocytes and CD3+ cells from patients with homozygous FH and heterozygous FH was similar to that of monocytes from a control population. Treatment with HMG-CoA reductase inhibitors did not affect the adherence to ICAM-1 or VCAM-1, and did not influence the expression of integrins.


CONCLUSIONS
In contrast to studies by others, we demonstrated in the present study that the actual LFA-1 and VLA-4 mediated adhesion of T-lymphocytes and monocytes is not altered in patients with FH.
de Bont
N
N
Department of General Internal Medicine, University Hospital Nijmegen, The Netherlands.
Geijtenbeek
T B
TB
Netea
M G
MG
Smilde
T J
TJ
Demacker
P N
PN
Figdor
C G
CG
Van Der Meer
J W
JW
Stalenhoef
A F
AF
D000293:Adolescent; D000328:Adult; D000924:Anticholesteremic Agents / Q000494:pharmacology; D001161:Arteriosclerosis / Q000209:etiology; D018821:CD18 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D006938:Hyperlipoproteinemia Type II; D039041:Integrin alpha4beta1; D019012:Integrin beta1 / Q000032:analysis; D016023:Integrins / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D009000:Monocytes / Q000502:physiology; D016201:Receptors, Lymphocyte Homing / Q000502:physiology*
D000924:Anticholesteremic Agents; D018821:CD18 Antigens; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D039041:Integrin alpha4beta1; D019012:Integrin beta1; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D016201:Receptors, Lymphocyte Homing