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© 1998 Oxford University Press

research-article

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

N. C. Hoglen*, S. P. Regan*, J. L. Hensel*, H. S. Younis*, J-M. Sauer*, D. R. Steup{dagger}, M. J. Miller{dagger}, S. J. Waterman{dagger}, L. E. Twerdok{dagger} and I. G. Sipes*,1

*Department of Pharmacology and Toxicology, Center for Toxicology, University of Arizona Tucson, Arizona 85721 {dagger}White Oils and Waxes Research Group, American Petroleum Institute Washington, DC 20005

Received December 23, 1997; accepted May 29, 1998

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 {gamma}-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.


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