Eosinophilic Inclusions in Rat Clara Cells and the Effect of an Inhaled Corticosteroid

Abstract

Large eosinophilic cytoplasmic inclusions (ECIs) are occasionally seen in untreated rat Clara cells. Following inhalation exposure to a corticosteroid, the number of ECIs was increased. This is the first histopathological description of rat ECIs and attempted characterization by immunohistochemistry, in situ hybridization, and electron microscopy. ECIs were strongly positive for surfactant protein D (SP-D) and weakly positive for Clara cell specific protein (CCSP). Clara cell cytoplasm was positive for CCSP mRNA regardless of ECIs, but not within ECIs. Corticosteroid treatment and ECI presence did not affect the immunohistochemistry and in situ hybridization staining intensities. Electron microscopy revealed large intracytoplasmic granules with an irregular limiting membrane. The ECI number was microscopically quantified in rats from three-, six-, and twenty-four-month studies. The mean ECI counts in treated rats increased from three- to fifty-four-fold with a positive dose-related trend, when compared with vehicle controls. Although the mechanism is unclear, SP-D and to a lesser extent CCSP accumulate in the ECIs. As human bronchial epithelium does not appear to contain structures analogous to the ECI, it is suggested that the observation of an increased number of ECIs in the treated rats is not likely to be relevant for human clinical risk assessment.

Giant Mitochondria in Pancreatic Acinar Cells of Alloxan-Induced Diabetic Rats

“…Giant cytoplasmic eosinophilic granules have often been observed in various cells under some pathological conditions and age-related changes. They are formed when cytoplasmic organelles such as endoplasmic reticulum, mitochondria, lysosome, secretory granules, and cytoskeleton are altered or increased (Herdson et al 1964; Horinouchi et al 1997; Ito et al 1998; Kambara et al 2009; Ozaki et al 1994; Remmer and Merker 1963). Eosinophilic inclusions or granules have also been detected as viral inclusion bodies and nuclear invagination (Kim et al 2002; Weller and Stoddard 1952).…”

Abdominal Teratoma in a Domestic Duck (Anas platyrhynchos domesticus)

“…They are thought to represent liposomes containing protein (Hard et al 1999). Large, eosinophilic, cytoplasmic inclusions are occasionally seen in untreated rat Clara cells (Kambara et al 2009).…”

Respiratory Tract

“…An increased number of these have been reported in rats treated with inhaled corticosteroids for periods of up to two years. 135 These inclusions are homogeneous, round, dense, eosin-stained globules in the cytoplasm of bronchiolar epithelial cells. They also stain with PAS.…”

“…110 They can also be visualized using immunohistochemical staining using antibodies for other cell constituents notably surfactant proteins and cytochromes P450. 108,135 Endocrine cells are visualized by immunocytochemistry using antibodies to general neuroendocrine markers such as chromogranin and synaptophysin or regulatory peptides. 114 Other useful antigens, which can be demonstrated in the lung, include surfactants, lysozyme, immunoglobulins and those of microorganisms that infect the lung.…”