Alteration of Kupffer Cell Function and Morphology by Low Melt Point Paraffin Wax in Female Fischer-344 but Not Sprague-Dawley Rats

• Published in: Toxicological sciences 1998-11, Vol.46 (1), p.176-184
• Main Authors: Hoglen, N. C., Regan, S. P., Hensel, J. L., Younis, H. S., Sauer, J-M., Steup, D. R., Miller, M. J., Waterman, S. J., Twerdok, L. E., Sipes, I. G.
• Format: Article
• Language: English
• ISSN: 1096-6080; 1096-0929
• DOI: 10.1093/toxsci/46.1.176

This study was conducted to compare the effects of 60-day dietary exposure (2%) to low melt point paraffin wax (LMPW) on both general liver morphology and Kupffer cell (KC) function and morphology in female F-344 and Sprague-Dawley (SD) rats. Livers from only F-344 rats fed LMPW had granuloma formation/lymphoid cell aggregates with small areas of necrosis. Significant increases in serum alanine and aspartate aminotransferase as well as γ-glutamyltransferase activities were detected only in treated F-344 rats. Additionally, detectable amounts of LMPW were present only in livers of treated F-344 rats. Because KC can be involved in granuloma formation, their morphology and function were examined. Electron microscopy revealed the presence of large, irregularly shaped, membrane-associated vacuoles in cells isolated from F-344 rats exposed to LMPW. These vacuoles were not seen in KC from control rats and rarely detected in KC isolated from LMPW-exposed SD rats. Moreover, indices of KC function including phagocytic activity and nitric oxide and superoxide anion production were significantly increased by KC isolated from F-344 rats exposed to LMPW (1.6-, 36-, and 2.2-fold increases, respectively) over untreated controls. In contrast, LPS-stimulated production of TNF and LTB4 was significantly decreased only in KC of LMPW-fed F-344 rats. No significant changes in these functions were observed in KC isolated from SD rats exposed to LMPW or from KC isolated from control F-344 or SD rats. These data provide evidence that dietary LMPW alters the morphology and functional capacity of KC of F-344 but not SD rats and these changes may ultimately lead to granuloma formation.