Mitotic activity in the dermis of mice during graft versus host disease: the role of fibroblast replication in dermal fibrosis.
When immunocompetent cells are transferred to an allogeneic, immunologically compromised host a complex series of cellular events are initiated, referred to as graft versus host disease. This results in widespread organ damage with fibrosis being a prominent feature. The pathologic fibrosis may result from an increase in fibroblast numbers, an increase in collagen produced from individual fibroblasts, or a combination of the two processes. The relative contribution of fibroblast replication to the pathologic fibrosis seen in graft versus host disease has not been directly determined previously, and this is the main object of this paper. Graft versus host disease was induced by the transfer of lymphoid cells from B10D2 mice to irradiated Balb/c recipients. In order to study the mitotic activity of dermal cells following bone marrow transplantation, a thymidine anologue, bromo-deoxyuridine (BrDU), was administered to mice using an osmotically driven, implantable infusion device. The labeled cells were visualized immuno-histochemically and studied at weekly intervals. There is intense mitotic activity in the basal layer of the epidermis and the acrosyringal epithelium from the second week. Evidence of increased mitotic activity in the epidermis persisted until the fifth week post-transplantation. Fibroblast replication was seen from the end of the third post-transplant week. Dermal collagen deposition also occurred at this time. Peak mitotic activity was present at the end of the fourth week and was less pronounced by the fifth week. It was especially evident in the upper dermis where the developing collagen layer was being deposited. To our knowledge this is the first direct demonstration of fibroblast proliferation in an immunologically mediated fibrotic disorder. It is concluded that fibroblast replication is an important mechanism leading to the pathologic fibrosis seen in graft versus host disease and, by analogy, probably other types of immunologically mediated fibrosis.
Katelaris
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A
Centre for Immunology, St. Vincent's Hospital, Sydney, Australia.
Penny
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Breit
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D000818:Animals; D001973:Bromodeoxyuridine / Q000494:pharmacology; D003094:Collagen / Q000032:analysis; D005347:Fibroblasts / Q000378:metabolism; D005355:Fibrosis / Q000473:pathology; D006086:Graft vs Host Disease / Q000503:physiopathology*; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D008938:Mitosis / Q000502:physiology*; D012867:Skin / Q000737:chemistry / Q000473:pathology; D012879:Skin Physiological Phenomena; D016038:Skin Transplantation / Q000473:pathology
D003094:Collagen; D001973:Bromodeoxyuridine