Immunoregulatory plasma lipoproteins. Role of apoprotein E and apoprotein B.
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.
D001053:Apolipoproteins / Q000097:blood / Q000276:immunology*; D001055:Apolipoproteins B; D001057:Apolipoproteins E; D001693:Biological Transport, Active; D002118:Calcium / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism; D010835:Phytohemagglutinins; D011485:Protein Binding
D001053:Apolipoproteins; D001055:Apolipoproteins B; D001057:Apolipoproteins E; D010835:Phytohemagglutinins; D002118:Calcium