Platelet-neutrophil conjugate formation is increased in diabetic women with cardiovascular disease.

BACKGROUND: More than seventeen million Americans are afflicted with diabetes and these people have four times the rate of coronary heart disease (CHD) as non-diabetics. Furthermore, diabetic women have a 3.8 fold greater risk for CHD compared to diabetic men. Little is known why diabetic women are at an increased risk for CHD. It is possible that diabetic women with cardiovascular disease (CVD) have a greater inflammatory response resulting in an increased platelet neutrophil conjugate formation than diabetic men with CVD or non-diabetic women with CVD. This study tested the hypothesis that platelet-neutrophil conjugates, which are associated with several cardiovascular diseases, are increased in diabetic women with CVD compared to diabetic men with CVD and non-diabetic women with CVD. METHODS: Platelet-neutrophil conjugates were quantified by flow cytometry. The primary method is through direct binding of the neutrophil PSGL-1 receptor with P-selectin expressed on the platelet. RESULTS: In this study, we found when the blood was stimulated with PAF (platelet activating factor), diabetic women without CVD demonstrated an increase in platelet-neutrophil conjugates compared to diabetic women with CVD and non-diabetic women with CVD (% conjugates: 63.3 +/- 5.2 vs 46.8 +/- 4.3 vs 48.6 +/- 3.4, p < 0.05). The stimulation ratio was significantly increased in diabetic and non-diabetic women with CVD in comparison to diabetic men with CVD (ratio: 3.3 +/- 0.4 vs 3.3 +/- 0.3 vs 2.1 +/- 0.3, p < 0.05). CONCLUSION: These results suggest that platelets and neutrophils in diabetic women have a greater potential for activation compared to diabetic men and may contribute to thrombosis/inflammation and the greater severity of coronary heart disease observed in diabetic women as compared to diabetic men.

Proinflammatory cytokines are increased in type 2 diabetic women with cardiovascular disease.

Diabetics have a much greater morbidity and mortality due to cardiovascular disease (CVD) than nondiabetics. Furthermore, diabetic women have a 3.8-fold greater risk for CVD compared to diabetic men. Inflammation is now considered a risk factor for CVD and it has been demonstrated that inflammation also plays a role in diabetes. One component of inflammation that has reported to be increased in patients with diabetes only and CVD only are proinflammatory cytokines, particularly interleukin-6 (IL-6), tumor necrosis factor (TNF-alpha), and interleukin-1 (IL-1beta). This study was performed to test the hypothesis that these proinflammatory cytokines were increased in women with CVD and further increased in diabetic women with CVD compared to nondiabetic women with CVD and healthy age-matched controls. We found that IL-6 was increased in diabetic women with CVD compared to healthy age-matched controls (1.41 = 0.48 to 0.33 +/- 0.06 pg/ml, P < .05). IL-6 was also increased in diabetic women without CVD compared to healthy age-matched controls, but not significantly (0.96 +/- 0.27 to 0.33 +/- 0.06 pg/ml). We found that TNF-alpha was increased in diabetic women with and without CVD compared to healthy age-matched controls, but not significantly (4.53 +/- 1.38 to 3.93 +/ -0.53 to 2.33 +/- 0.89 pg/ml). IL-1beta was not significantly different among any of the four groups of women. These results indicate that both IL-6 and TNF-alpha are chronically increased in diabetic women with and without CVD compared to nondiabetic women. The additive concentration of cytokines in diabetes and CVD suggests a common inflammatory state in both diabetes and CVD.

Neutrophil activation by murine retroviral infection during chronic ethanol consumption.

AIMS: Neutrophil adhesion molecule CD11b and reactive oxygen species (ROS) are neutrophil activation markers for evaluating the functional activity of neutrophils. The aim of this study was to determine if neutrophils are activated in murine AIDS and/or chronic ethanol consumption and if neutrophil CD11b expression and ROS production vary when progressive retrovirus infection occurs. METHODS: Four groups were studied: control, murine AIDS, ethanol and ethanol plus murine AIDS. Neutrophil activation was assessed by CD11b expression and ROS production using flow cytometry. RESULTS: We found that neutrophils lost their responsiveness to fMLP due to retrovirus or ethanol exposure. In the murine AIDS group, neutrophil CD11b expression was up-regulated along with a significant increase in ROS after 1 month of retroviral infection. After 2 months, neutrophil CD11b and ROS decreased. However, neutrophil CD11b expression further increased after 3 months. In the ethanol consumption group, neutrophil CD11b expression was down-regulated after 2 months, whereas ROS production increased in the first and third months. In the murine AIDS plus ethanol group, there were significant increases in both ROS and CD11b expression during the 3-month observation period. CONCLUSIONS: These findings suggest that neutrophil function is impaired by LP-BM5 retrovirus infection and/or chronic ethanol consumption. The pattern of neutrophil CD11b expression and ROS production might help to predict the stage of murine AIDS. Ethanol may further compromise neutrophil function in AIDS.