The immunohistochemical heterogeneity of atheroma macrophages: comparison with lymphoid tissues suggests that recently blood-derived macrophages can be distinguished from longer-resident cells.

Abstract

We studied the antigenic markers of macrophages (Mphs) in atherosclerotic human arteries by immunohistochemistry and compared them with the patterns in Mph subpopulations of tonsil and lymph node, which are also described. The staining of atheroma intimal Mphs was assessed semiquantitatively in the subendothelial, mid, and outer intima. Three patterns of reactivity with Mph antibodies were recognized. (a) Pan-Mph (antibodies HAM56, EBM11, and CD14 group). Staining was maximal in the mid-intimal zone. (b) Subendothelial Mphs (anti-muramidase, anti-alpha-1-antitrypsin and MAC387). In lymphoid tissue, sinusoidal Mphs and a few inflammatory Mphs were stained, as well as blood monocytes. This group of antibodies recognizes Mphs that are likely to be recently blood-derived (RBD-Mphs). (c) Antibodies reactive with various histiocyte populations in lymphoid tissues (anti-Factor XIII; anti-HLA Class II and LN2) also gave maximal staining in the mid-intimal zone, but differences between lesion types suggest that they are recognizing heterogeneous subpopulations of Mphs. These observations demonstrate the heterogeneity of tissue Mphs and suggest that an insight into the dynamics of tissue Mphs can be obtained from the cell phenotype. They indicate that all stages of atherosclerosis can have an outward traffic of Mphs from the blood through the arterial intima.

Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata

“…The observation that Ly-6C hi cells trafficked differentially to lesions supports the concept of heterogeneity of atheromata (47,48) and suggests that these cells migrate preferentially to lesions of high inflammatory activity. Interestingly, fatty streaks harbored few Ly-6C hi monocytes, indicating low monocyte accumulation at this stage.…”

Macrophage Differentiation and Function in Atherosclerosis: Opportunities for Therapeutic Intervention?

“…This heterogeneity in atherosclerosis has long been recognized [33], and macrophages expressing markers of M1 and M2 activation have been demonstrated in murine and human plaques [34, 35]. Furthermore, macrophages are known to be plastic cells that retain their ability to respond to their microenvironment, and change their phenotype, once differentiated.…”

Heterogeneity of Human Macrophages in Culture and in Atherosclerotic Plaques

“…In concordance with this hypothesis, previous studies have demonstrated heterogeneity among the macrophages infiltrating human atherosclerotic lesions. 10 However, the functional role of these heterogeneous macrophage subpopulations in the pathogenesis of atherosclerotic disease has not yet been elucidated.…”