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Morphology and immunohistochemistry of rat aortic grafts

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Abstract

Allotransplantation (TPL) of the abdominal aortic segments of BN donors was performed in 32 Lewis recipients with or without cyclosporin A (CyA) immunosuppression, and the vascular changes were compared to those of 10 syngeneic grafts (Lewis→ Lewis) and to the autologous rat aortae. The vessels were examined 2, 3, 4 and 5 months post TPL by light microscopy, the thickness of intima and media was measured morphometrically and the cell infiltration of adventitia and intima was assessed semiquantitatively. Thirty-six aortae were examined by three-step enzyme immunohistochemistry (proof of selected differentiation, proliferation, cytoskeletal and connective tissue matrix antigens). The adventitia displayed an intense focal and scattered mononuclear cell infiltration: it was more discrete and focal in the intima. This cellularity persisted in the allografts but disappeared from the intima and was reduced in the adventitia of the isografts after four and five months. Disseminated EDI+ activated macrophages were the most prominent population of infiltrates whereas modest numbers of adventitial ED2+ tissue macrophages remained constant throughout the intervals examined CD4+ cells (focal and scattered) outnumbered (roughly twice) the scattered CD8+ lymphocytes; both these types were rare in the intima. Leukocyte invasion of the media was lacking (except for scarce isolated CD8+ cells in some allografts). In syngeneic grafts the smooth muscle cells (SMC) of media remained intact and the intimal thickening was slight to absent (about 5 μm) four and five months post TPL. On the other hand, the allograft media underwent severe destructive changes (karyolysis, depletion of α-SMC actin, focal calcification and general thinning without rupture or aneurysm). The prominent allograft intimal thickening (70–80 μm) was due to the proliferation of longitudinally oriented myointimal cells (α-SMC actin, ED2, PCNA and Ki67+) and an increase in matrix substance (strong metachromasia and positivity of chondroitin-sulfate proteoglycan). The deposition of lipids remained discrete, without atheromatous plaques and mural thrombosis. All changes were comparable in CyA-treated and untreated animals.

Thus the main lesions of the allografts were (i) persistent mononuclear infiltration chiefly in adventitia, (ii) destruction of medial SMC, and (iii) intimal thickening by proliferation of myointimal cells. At the post TPL intervals examined the proliferation and intimal migration of medial SMC were not apparent and a morphological correlate of significant anti-medial-SMC cytotoxic attack was lacking.

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Abbreviations

ASMA:

α isoform of smooth muscle cell actin

CHSPG:

chondroitin sulfate-proteoglycan

CyA:

cyclosporin A

DAB:

3,3′-diaminobenzidin-tetrahydrochloride

EA:

endarteritis

HAM:

anti-mouse-lg antibody produced in horse

mAb:

monoclonal antibody

PAS:

periodic acid-Schiff staining

PCNA:

proliferating cell nuclear antigen (cyclin)

PDGF:

platelet-derived growth factor

SMC:

smooth muscle cell(s)

TPL:

transplantation

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Authors and Affiliations

  1. Institute of Microbiology, Academy of Sciences of the Czech Republic, 142 20, Prague

    P. Rossmann

  2. Department of Nephrology, Transplant Center of the Institute for Clinical and Experimental Medicine, 140 21, Prague, Czech Republic

    L. Lácha

  3. Department of Pathology, Transplant Center of the Institute for Clinical and Experimental Medicine, 140 21, Prague, Czech Republic

    A. Lodererová

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  1. P. Rossmann
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  2. L. Lácha
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  3. A. Lodererová
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Correspondence to P. Rossmann.

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Rossmann, P., Lácha, L. & Lodererová, A. Morphology and immunohistochemistry of rat aortic grafts. Folia Microbiol 44, 339–353 (1999). https://doi.org/10.1007/BF02818558

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