Response of bronchiolar Clara cells induced by a domestic insecticide. Analysis of CC10 kDa protein content

Clara cells are the most reactive to xenobiotics among the mammalian respir atory tract cells. In this report, the response of Clara cells to acute or repetitive exposure to a commercial insecticide was studied, correlating th e changes in the cell ultrastructure with the intracellular content of CC10 kDa protein as quantified by immunocytochemical morphometry. After a singl e exposure to insecticide, Clara cells reveal great expansion of their volu me which is accompanied by a remarkable proliferation of smooth endoplasmic reticulum, swelling of the mitochondria ia, and changes in the nucleus. Mo rphometric analysis of CC10 bronchiolar content showed significant increase s in both the number of Clara cells and the immunostained areas in individu al cells. By western blot, CC10 immunoreactive bands strongly increased in lungs after insecticide treatment, but they were only slightly higher than the control when the vehicle of the insecticide was tested. By repetitive e xposure to the insecticide, the rat bronchiolar epithelium undergoes extens ive alterations, particularly on Clara cells, the number of which is consid erably reduced. The remaining Clara cells shrink in size and the typical do me-like cytoplasm is lost. Secretory granule release is no longer seen and the changes of their shape and secretory content reflect a marked degradati on and condensation process. Repetitive exposures to the insecticide produc ed a severe blockage of the proteinopoietic activity. particularly on the s ynthesis of CC10. Results reported here reveal that the acute inhalation of a commercial insecticide produces hypertrophy of Clara cells, a significan t augmentation of CC10 synthesis, and probably differentiation de novo of C lara cells, and morphological changes compatible with a detoxification proc ess. By contrast, exposure for 5 days provoked a general inhibitory effect on Clara cell activity with the loss of cell capability to synthesize and s ecrete CC10 kDa protein.