Diagnostic assessment of macrophage phenotypes in cardiac transplant biopsies

Abstract

Forty-one endomyocardial biopsies of the right interventricular septum have been investigated in 24 immunosuppressed patients after orthotopic heart transplantation. Monoclonal antibodies 27E10, 25F9, and RM3/1, which react with different macrophage phenotypes, and antisera MRP-8 and MRP-14, specific for proteins expressed on endothelial and monocyte cell surfaces in inflammation as well as markers for CD4+ and CD8+ T-lymphocytes, were employed in an indirect immunoperoxidase staining technique. This methodology permits more physiological recognition of the inflammatory process within the myocardium. It was possible to verify and to distinguish acute early, late and down-regulatory stages of inflammation in 33 biopsies (80%). No evidence of inflammation was found in seven biopsies (17%). Conventional histopathology with haematoxylin-eosin and Masson's trichrome was performed simultaneously, and demonstrated inflammation to be present in 23 of 41 biopsies (56%). An important findings is that CD4+ and CD8+ lymphocytes were absent in 15 of 41 specimens (37%) although there was inflammation proven by the presence of different macrophage phenotypes. The results indicate the necessity of long-term serial investigations of the physiological role of specific inflammatory macrophage phenotypes during the rejection process. It is concluded that the phenotyping of macrophage and endothelial cell differentiation antigens offers a sensitive approach to assess diagnosis of myocardial inflammation as a consequence of ongoing rejection in cardiac allografts.

The calcium‐binding proteins MRP8 and MRP14 form a membrane‐associated heterodimer in a subset of monocytes/macrophages present in acute but absent in chronic inflammatory lesions

“…In acute inflammatory lesions, the monocytes seem to differentiate further and to assemble the heterodimer bearing the 27E10 epitope. This observation has been confirmed by the results obtained from psoriasis vulgaris [ 3 ] , periodontitis [4] and cardiac allografts [39]. In a recent study on a series of rejections of renal allografts (Goebeler et al, manuscript in preparation), in chronic rejections as well as in other chronic conditions (colitis ulcerosa, theumatoid arthritis, sarcoidosis, multiple sclerosis, Alzheimer's disease, own unpublished data), one also observes the influx of MRP8+ and MRP14+ cells, yet, the 27E10 epitope is rarely or not at all formed.…”

Infiltration patterns of macrophages and lymphocytes in chronically rejecting rat kidney allografts

“…In human renal allografts undergoing chronic rejection, subendothelial blaques consisting of macrophages in f o a w transformation have been described [22]. Macrophages of various phenotypes have been noted in biopsies of heart allografts [18], while intimal foam cells derived mostly from macrophages, and to a lesser extent from smooth muscle cells, almost completely occupied the coronary lumina of heart grafts in cholesterol-fed and immunosuppressed rabbit recipients [23]. These results imply that not only immunological factors are involved in the reaction of the arterial wall in transplant arteriopathy but that, as in atherosclerosis, endothelial dysfunction may also be important [22].…”

Early infiltration of renal allografts with 27E10-positive macrophages and graft outcome

“…In all inflammation models tested so far, 27 E 10-positive macrophages are the first to arrive at the lesion [l]. They have been described in acute heart [3], liver [4] and renal allograft rejection [5,6].…”