Neutrophil association and degradation of normal and acute-phase high-density lipoprotein 3

The interaction of normal and acute-phase high-density lipoproteins of the subclass 3 (N-HDL₃ and AP-HDL₃) with human neutrophils and the accompanying degradation of HDL₃ apolipoproteins have been studied in vitro. The chemical composition of normal and acute-phase HDL₃ was similar except that serum amyloid A protein (apo-SAA) was a major apolipoprotein in AP-HDL₃ (approx. 30% of total apolipoproteins). ¹²⁵I-labelled AP-HDL₃ was degraded 5-10 times faster than ¹²⁵I-labelled N-HDL₃ during incubation with neutrophils or neutrophil-conditioned medium. Apo-SAA, like apolipoprotein A-II (apo-A-II), was more susceptible than apolipoprotein A-I (apo-A-I) to the action of proteases released from the cells. The amounts of cell-associated AP-HDL₃ apolipoproteins at saturation were up to 2.8 times greater than N-HDL₃ apolipoproteins; while apo-A-I was the major cell-associated apolipoprotein when N-HDL₃ was bound, apo-SAA constituted 80% of the apolipoproteins bound in the case of AP-HDL₃. The associated intact apo-SAA was mostly surface-bound as it was accessible to the action of exogenous trypsin. α₁-Antitrypsin-resistant (α₁-AT-resistant) cellular degradation of AP-HDL₃ apolipoproteins also occurred; experiments in which pulse-chase labelling was performed or lysosomotropic agents were used indicated that significant intracellular degradation occurred which points to the involvement of cell-surface proteases in this degradation.