In vivo transmigrated monocytes from patients with stable coronary artery disease have a reduced expression of CD11b

Abstract

Coronary artery disease (CAD) is characterized by infiltration of monocyte derived cells in the intima of the vessel wall. We hypothesized that accumulation of these cells is caused partly by an altered monocyte transmigration process in CAD. To gain insight into this issue we applied the skin blister method that allows collection of in vivo transmigrated cells at sites of local inflammation. Nineteen patients with stable CAD and 19 matched controls were enrolled. Markers of inflammation and gradients of chemokines, as well as adhesion molecule expression and up-regulation capacity, were studied. The expression of inflammatory markers, such as C-reactive protein, interleukin (IL)-6, tumour necrosis factor-alpha and IL-10, was similar in patients and controls, indicating that patients were in a stable phase of the disease. Expression of adhesion molecules, CD11b and very late activation antigen-4, on peripheral monocytes did not differ between patients and controls. However, following in vivo transmigration, monocytes in patients with CAD had a significantly reduced expression and mobilization of CD11b. The effect on CD11b could not be reproduced by in vitro stimulation with blister fluid, representing a local inflammatory milieu, or in an in vitro system of transmigration. These findings point towards differences in monocyte CD11b expression and availability at an inflammatory site between patients with CAD and healthy controls.

Fig. 1

Number of transmigrated cells in the unstimulated, intermediately stimulated (phosphate-buffered saline) and intensely stimulated (serum) blisters. There were no significant differences between patients and controls. The number of transmigrated cells increased significantly with the degree of inflammation. ***P < 0·005.

Fig. 2

Expression of CD11b on peripheral and transmigrated cells. Patients had significantly lower expression of CD11b compared with controls in the unstimulated blister (P = 0·002).

Fig. 3

CD11b mobilization on peripheral and transmigrated cells after additional stimulation with formyl-Met-Leu-Phe. Patients had lower mobilization of CD11b compared with controls in both the intermediately stimulated blister (P = 0·04) and the intensely stimulated blister (P = 0·006).

Fig. 4

The effect of in vivo transmigration on CD11b expression, shown as the ratio of CD11b between blister and blood. In the intermediately stimulated (phosphate-buffered saline) blister P = 0·04 and in the intensely stimulated (serum) blister P = 0·02.

Fig. 5

CD11b mobilization on transmigrated cells following formyl-Met-Leu-Phe stimulation expressed as the ratio of CD11b between blister and blood. In the intermediately stimulated (phosphate-buffered saline) blister P = 0·008 and in the intensely stimulated (serum) blister P = 0·003.