E G Shephard

C‐reactive protein and serum amyloid A protein in pregnancy and labour

Summary. Serum levels of C‐reactive protein (CRP) and amyloid A protein (SAA) were measured prospectively using immunoradiometric assays in normal pregnant women, newborn infants and women with prelabour rupture of membranes (PROM), focusing on the peripartum period. CRP levels in 50 healthy women at 38 weeks gestation did not differ significantly from previously established normal values. CRP levels in 67 healthy women sampled serially in labour from admission to 96 h postpartum confirm the physiological occurrence of a major acute phase response. The serial CRP levels of 16 women with PROM did not differ significantly from the wide range of CRP levels found in the normal postpartum period. This complicates the use of CRP as an early predictor of clinical chorio‐amnionitis. Serial SAA levels in 17 women at 38 weeks gestation, immediately postpartum and 24 h postpartum showed a parallel rise to CRP in the peripartum period. Significant differences between maternal and neonatal CRP and SAA levels were demonstrated, implying a lack of transplacental transfer during labour.

Interaction of liposomes with human leukocytes in whole blood

The uptake of multilamellar liposomes into human leukocytes in whole blood in vitro was evaluated on the basis of the cellular association of liposomal markers (3H-labelled cholesterol, lipid phase; [14C]inulin, aqueous phase). The entry of liposomes into human blood leukocytes was linear for 60 min and was mediated by a saturable mechanism displaying affinity constants of 0.28 +/- 0.17 and 0.16 +/- 0.05 mM liposomal lipid (means +/- S.E.) for liposomal lipid and aqueous phase markers, respectively. Amicon filtration analysis of incubation mixtures containing blood and liposomes (phosphatidylcholine:dicetyl phosphate:cholesterol, 70:20:10) showed that 34% of [14C]inulin was lost (neither liposome-associated nor cell-associated) after 60 min. By preincorporating sphingomyelin (35 mol%) into multilamellar liposomes, the leakage of the model aqueous phase marker inulin was reduced to 8% after 60 min, thus enhancing the drug carrier potential of liposomes in blood. As a consequence of their interaction with liposomes, the polymorphonuclear leukocytes in whole blood decreased in apparent buoyant density, while maintaining their viability. These results indicate that blood leukocytes in their natural milieu of whole blood are capable of interacting with, and taking up multilamellar liposomes.

Biosynthesis and Processing of SAA by Mouse L-Cells Transfected with the Human SAAg9 Gene

Pulse-chase studies of SAA biosynthesis and processing in mouse L-cells transfected with the SAAg9 gene have shown that, over a 2h time period, intracellular SAA does not show amino-terminal trimming. Extracellular SAA, although principally composed of the pI=8.0 isoform, shows limited conversion from the pI=8.0 to pl=7.4 isoform over a 2h period.

Structure, Metabolism and Function of Acute Phase High Density Lipoprotein

The acute phase response is a multi-system adaptation induced by autologous cell death or by products of exogenous invasion (Kushner 1982). These influence macrophages to secrete various monokines that, among other functions, affect hepatic gene expression for many proteins (Ramadori et al. 1985). This response consists of a variety of biochemical, cellular, hormonal and metabolic changes with characteristic increases in many plasma proteins. Serum amyloid A protein (apo-SAA) is particularly notable in that it is normally present in trace amounts in human serum, but the concentration increases up to 100-fold within 48 hours of initiation of the acute phase. (Eriksen and Benditt 1984; McAdam et al. 1978; de Beer et al. 1982). Segrest et al. (1976) first noted that a 45-residue fragment of the apo-SAA cleavage product, amyloid A protein (AA), formed stable complexes with phospholipid. This finding preceded the discovery, by Benditt and Eriksen (1977), that apo-SAA is transported in human plasma mainly with high density lipoproteins (HDL) and is thus classified as an apolipoprotein. Although HDL (expressed as HDL cholesterol) is a significant negative acute phase reactant, it can play a role in inflammation. HDL has been reported to function as a vehicle to transfer damaged cellular constituents to the liver and to bind bacterial lipopolysaccharides (Ulevitch et al. 1981) and neutrophil elastase (Jacob et al. 1981). The function of apo-SAA rich HDL in response to injury is, however, unknown. The phylogenetic conservation of the association of apo-SAA with HDL suggests that it plays an important role.