Immunoregulatory plasma lipoproteins. Role of apoprotein E and apoprotein B

J Biol Chem. 1980 Dec 25;255(24):11775-81.

Abstract

Plasma lipoproteins containing either the B (apo-B) or E (apo-E) apoproteins, e.g. apo-B low density lipoproteins (LDL) isolated from normolipemic humans and apo-E-containing cholesterol-induced high density lipoproteins (apo-E HDLc) isolated from cholesterol-fed dogs, suppress phytohemagglutinin (PHA)-induced lymphocyte activation and inhibit early events such as mitogen-enhanced 45Ca2+ accumulation and late events such as enhanced DNA synthesis. On a molar basis, apo-E HDLc are 3.5 times more effective than apo-B LDL in inhibiting 45Ca2+ accumulation by 50% and 3.8 times more effective than apo-B LDL in suppressing DNA synthesis by 50%. Both lipoproteins bind to the lymphocyte surface, and in competitive binding assays apo-E HDLc and apo-B LDL bind to the same receptors. These receptors, termed immunoregulatory receptors, comprise a homogeneous class of binding sites which do not act cooperatively. The equilibrium dissociation constant (Kd) for apo-B LDL is 2.0 X 10(-7) M at 4 degrees C and 37 degrees C; the Kd for apo-E HDLc is 9.3 X 10(-8) M at 4 degrees C and 7.3 X 10(-8) M at 37 degrees C. At saturation, 16,000 and 20,000 LDL particles are bound/cell at 4 degrees C and 37 degrees C, respectively. The corresponding values for apo-E HDLc are 6,700 at 4 degrees C and 5,500 at 37 degrees C. The increased effectiveness of apo-E HDLc in supp]ressing the PHA-induced Ca2+ accumulation and DNA synthesis is due to the multiple receptor binding of apo-E HDLc. At 37 degrees C, each apo-E HDLc particle occupies multiple receptors at a ratio of 3.6:1 relative to apo-B LDL. The enhanced affinity of apo-E HDLc most likely results from the multiple interactions of this lipoprotein with the receptors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apolipoproteins / blood
  • Apolipoproteins / immunology*
  • Apolipoproteins B
  • Apolipoproteins E
  • Biological Transport, Active
  • Calcium / metabolism
  • Humans
  • Kinetics
  • Lymphocyte Activation
  • Lymphocytes / immunology*
  • Lymphocytes / metabolism
  • Phytohemagglutinins
  • Protein Binding

Substances

  • Apolipoproteins
  • Apolipoproteins B
  • Apolipoproteins E
  • Phytohemagglutinins
  • Calcium