Yoneyama H, Kawanami O, Usuki J, Furuta T, Ohkuni H, Todome Y, Ooami H
Pathology and Clinical Research Laboratory, Nippon Medical School Second Hospital.
Arerugi. 1993 Aug;42(8):955-62.
Experimental silicosis was induced by intratracheal infusions of 1 ml saline containing 50 mg standard silica (less than 5 microns diameter) in Sprague-Dawley rats. The lung tissues were observed histologically and ultrastructurally from half an hour up to 4 months. Macrophages, neutrophils, desquamated cells and their debris piled up around the alveolar ducts where the central cores of silicotic granuloma appeared. The granuloma became apparent by day 4 after the infusion and were covered by type II alveolar epithelial cells and bronchiolar cuboidal epithelial cells. Macrophages, fibroblasts and epithelial cells began to react to the antibody against proliferating cell nuclear antigen (PCNA) indicating self-replication on day 1. Macrophages in the granuloma made a close interdigitation with adjacent macrophages, and they gradually formed subplasmalemmal linear densities (SPLD) as paired forms between adjacent plasma membranes, and unpaired forms facing the interstitial matrix. SPLD were composed of linear densities with actin-like microfilaments along the leaflets of plasma membrane and were associated with extracellular dense bands which resembled a limited length of basement membrane. Interdigitation and SPLD structures were quite rare on day 1, but the number of macrophages with both structures increasingly appeared. The frequency of SPLD in macrophages also increased on a time course of granuloma maturation up to 4 months. Thus SPLD, which were originally found in the mononuclear phagocytes including macrophages, epithelioid cells and multi-nucleated giant cells, particularly in immune granuloma of man, also played a basic role in immobilizing macrophages in lesions of silica-induced granulomas.