THE IN VITRO FUNCTIONS OF NORMAL PERIPHERAL LYMPHOCYTES ARE INFLUENCED BY LOW MOLECULAR WEIGHT HEPARINES
Opinion: THE IN VITRO FUNCTIONS OF NORMAL PERIPHERAL LYMPHOCYTES ARE INFLUENCED BY LOW MOLECULAR WEIGHT HEPARINES
M. Neagu1, G. Manda1, M. Gaghes1, C. Constantin1,
C. Tanaseanu2. 1Immunology Department, Victor Babes National Institute, Bucharest, Romania, 2Sf. Pantelimon Emergency Hospital, Bucharest, Romania
Aim: Evaluation of the in vitro proliferative capacity of normal peripheral lymphocytes in presence of various commercial low molecular weight heparins (LMWH) in order establish the prevention potential of the compounds and the effects on the immune cell population. The most frequently new generation of anticoagulants used in the treatment of cadiovascular diseases were studied.
Donors. Healthy volunteers (n=50), average body weight, ages 35±15, 57% females, 43% males, no medication, no clinical sings of any illness at the investigation moment and with no present or family cardiovascular symptoms were investigated.
LMWH. Fraxiparine (Sanofi), Fragmin (Pharmacia&UpJohn AB), Clivarin (Knoll), Innohep (Leo Laboratories), Clexan (Bel- lon France) were tested in the range of 0.06–600 UAXa/ml (doses that match the therapeutical range).
Methods: Peripheral cells were isolated on Hystopaque gradient centrifugation. The proliferative capacity of unstimulated or mitogen (phytohaemagglutinine M – PHA or pokeweed mitogen – PWM) stimulated lymphocytes was assessed with H3-Td incorporation method in presence and absence of LMWH.
Results: All the tested LMWH induced with various intensities an activation of the proliferative capacity of unstimulated lympho- cytes. 0,6UAXa/ml Fraxiparine induced the highest activation in vitro. We found that the activation capacity of Fraxiparine was higher on the subgroup of normal subjects that displayed lower basal proliferative capacity. In the costimulation systems with PHA, Frax- iparine induced significant inhibition of the proliferation capacity of policlonaly-stimulated lymphocytes in the tested concentration range. In the costimulation systems with PWM, only 6UAXa/ml Fraxiparine significantly reduced the proliferative capacity of normal peripheral lymphocytes. No effects were registered in the mentioned systems in presence of the other mentioned LMWH.
Conclusions: Fraxiparine probably hinders the mitogen binding on T- and B-lymphocytes. Due to the registered in vitro effect, LMWH can influence the proliferative capacity of normal lym- phocytes and consequently alter the immune response. The study emphasize on the relation between the particularity of the normal immune cells functionality and the in vitro registered effect of LMWH.
RESISTANCE TO IN VITRO INFECTION WITH LEISHMANIA MAJOR IN MACROPHAGES FROM ARYL HYDROCARBON RECEPTOR-NULL MOUSE
L. Vega 1 , M.I. Vázquez 1 , M. Rodríguez 2 , G. Elizondo 1 . 1 Sección Externa de Toxicología, Centro de Investigación y Estudios Avanzados-IPN. 2Instituto Nacional de Cardiología, México D. F., México
Aryl hydrocarbon receptor (AhR) is a basic helix-loop-helix tran- scription factor that is activated by ligand binding and dimerization with AhR nuclear translocator (ARNT) in response to xenobiotics. AhR mediates transcriptional activation of several genes encoding xenobiotic-metabolizing enzymes such as CYP450 1A1 and 1A2.