Modulation by lipoproteins of amphotericin B-induced immunostimulation

Abstract

Previous reports indicate that amphotericin B (AmB) and amphotericin methyl ester (AME) are potent adjuvants and polyclonal B-cell activators, and that most mouse strains can be classified as high or low responders to AmB and AME. In the present study, an inbred strain with very high plasma cholesterol concentration (HC strain) proved to be a low responder. Responses of HC mice to other immune stimuli were normal, suggesting that HC lymphoid cells expressed selectively weak responses to AmB and AME. Plasma levels of low-density lipoproteins (LDL), very-low-density lipoproteins (VLDL), and high-density lipoprotein subfraction (HDL 2) were very much higher in HC mice than in AKR mice, an AmB-high responder strain. Low responses in vitro to AME were observed with lymphoid cells from HC mice and from AKR → HC bone marrow chimeras, i.e., AmB-high responder strain lymphocytes from a low responder host. However, enhanced AME responses were induced by a 2- or 48-hr preincubation of splenocytes from either HC or AKR mice in medium containing lipoprotein-depleted fetal calf serum. Taken together these studies indicate that plasma lipoproteins can inhibit lymphocyte responses to AME; this seems to account for the low AmB and AME responses of the HC strain. The mechanism of this lipoprotein-induced inhibition remains obscure, but it cannot be accounted for by competitive binding of AmB by lipoproteins.