Genetic control of macrophage functions. I. Polygenic regulation of phagocytosis stimulation produced by glyceryl trioleate

Abstract

The phagocytic index K, established from the rate of blood clearance of colloidal carbon, measures the phagocytic activity of RE macrophages in contact with the circulating blood. The intravenous injection of glyceryl trioleate (triolein) produces a marked stimulation of the phagocytic activity of RE macrophages. This response is higher in female than in male mice. The phenotypic character 'responsiveness of macrophage to triolein' presents large individual variations in population of random bred albinos mice. This character is submitted to polygenic regulation. Starting from a foundation population of 25 males and 25 females random bred albinos mice, 2 lines were separated by selective breeding for the single responsiveness to triolein': a 'high' responder line, KTH, and a 'low' responder line, KTL. After 26 consecutive generations of selective breeding, KTH mice present a very high response to triolein while KTL mice are almost irresponsive. The heritability of this character (h2) calculated from the interline divergence is of 12% ± 1. This value of h2 indicates that the character investigated is determined by the cumulative effect of a group of about 27 independently segregating loci. The distribution of the character in (KTH x KTL)F1 and their backcrosses with parental lines suggests that low responsiveness is dominant over high responsiveness. The genetic regulation of responsiveness to triolein is independent from the dose administered. The results are discussed in relation to the importance of genetic factors controlling macrophage functions involved in lipid metabolism and in the specific and nonspecific mechanisms of immunity.