ABSTRACT
Background: immune cells participate in the formation of atheromatous plate, however little is known about the effects of native or oxidatively modified lipoproteins on these cells. Aim: To study the effects of lipoproteins on in vitro mononuclear cell proliferation. Material and methods: peripheral blood mononuclear cells were obtained from 10 patients with type 2 diabetes mellitus (aged 52 ñ 9 years old with a disease duration of 8.2 ñ 5.7 years and a mean glycosilated hemoglobin of 9.3 ñ 2.2 percent) and 10 non diabetic healthy controls (aged 50.3 ñ 7.1 years old). These were stimulated with phytohemagglutinin (PHA) alone or in the presence of native LDLS, malondialdehyde modified LDLs or glycated LDLs. Proliferation was measured as 3H-thymidine incorporation and expressed as Stimulation Index (SI). Results: SI of patients and healthy subjects, after PHA stimulation were similar: (57.5 ñ 29.8 and 61.1 ñ 23.5) respectively LDLs did not induce proliferation in neither group. Native LDLs produced a 98 percent inhibition of PHA induced proliferation. Malondialdehyde modified and glycated LDLs caused a 50 percent inhibition. The suppressive effect was maintained when lipoproteins were incorporated to culture media 60 min prior or after PHA stimulation. Conclusions: Lipoproteins inhibit in vitro PHA induced peripheral blood mononuclear cell proliferation both in diabetic and in non diabetic subjects
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Diabetes Mellitus, Type 2/immunology , Immunosuppression Therapy , In Vitro Techniques , Lipoproteins, LDL/immunology , Phytohemagglutinins/pharmacology , Lymphoproliferative Disorders/immunology , Lymphocyte ActivationABSTRACT
LDLs obtainded from blood of healthy subjects, were glycated or altered with malondialbehyde and used as antigens. Serum autoantibodies against these LDLs were measured by ELISA in 22 patients with non insulin dependent diabetes mellitus aged 46 to 67 years old and 13 healthy controls aged 41 to 64 years old. Basal and LDL stimulated tumor necrosis factor production in vitro, by peripheral leukocytes of diabetics and controls was also measured. Results: The ratio of glycated LDL/native LDL antibodies was higher in diabetics than in controls (9.37 ñ 2.72 and 0.41 ñ 0.11 respectively p < 0.05) and the ratio of MDA modified LDL/native LDL antibodies was not significantly different (8.64 ñ 3.83 and 2.14 ñ 1.26 respectively, NS). Tumor necrosis or production by leukocytes was higher in diabetics than in controls in basal conditions (53.3 ñ 15.3 and 26.9 ñ 14.7 arbitrary units (a.u.) respectively), when stimulated withnative LDL (46.5 ñ 5 and 24.3 ñ 9.4 a.u. respectively), when stimulated with malondialdehyde modified LDL (50 ñ 16.2 and 24.4 ñ 7.7 a.u. respectively) or when stimulated with glycated LDL (38.3 ñ 8.8 and 14.4 ñ 7.5 a.u. respectively). Conclusions: Diabetic patients have an enhanced immune response against low density lipoproteins, factor that could contribute to the accelared atherogenesis of this disease