CELLULAR HETEROGENEITY IN BINDING AND UPTAKE OF LOW-DENSITY-LIPOPROTEIN IN PRIMARY RAT HEPATOCYTES

Hepatocellular heterogeneity of biochemical function is well establish ed for many aspects of liver metabolism. This study addresses the ques tion of cellular heterogeneity in the catabolism of low-density lipopr otein by rat hepatocytes. Low-density lipoprotein binding (4-degrees-C ) and uptake (37-degrees-C) by rat hepatocytes were studied by use of human low-density lipoprotein labeled with a highly fluorescent lipoph ilic probe, N,N-dipentadecylaminostyrylpyridinium iodide, recently dev eloped by us. Single-cell suspensions derived from rat hepatocytes in primary culture and from liver perfusion were studied with flow cytome try with and an approximation algorithm for data analysis. These studi es show subpopulations of cells negative and positive for the specific binding and uptake of low-density lipoprotein. Dissociation constants for low-density lipoprotein binding and uptake were determined for th e total population (18 mug/ml, binding; 12 mug/ml, uptake) and found t o be in good agreement with previously reported values. Additionally, the dissociation constant for binding for the positive subpopulation w as determined and found to be 3 mug/ml. This lower value is more typic al of the values seen in other cell types. These findings are strongly suggestive of functional heterogeneity in the hepatic catabolism of l ow-density lipoprotein.