Jon C. Lewis

Resistance to Arteriosclerosis in Pigs with von Willebrand's Disease: SPONTANEOUS AND HIGH CHOLESTEROL DIET-INDUCED ARTERIOSCLEROSIS

The aortas of 11 pigs (aged 1-3 yr) with homozygous von Willebrands disease (vWd) were compared with those of 11 normal pigs of the same ages. Six of the controls exhibited multiple arteriosclerotic plaques with intimal thickening of 63-130 mum. In contrast, none of the pigs with vWd had multiple plaques, and only one had a lesion >2 mm in diameter. In a subsequent study, 3-mo-old pigs (11 controls and 7 with homozygous vWd) were placed on a 2% cholesterol diet for up to 6 mo. All of the controls developed arteriosclerotic plaques in the aorta, and in nine of the controls, at least 13% of the entire surface was involved. Intimal thickness ranged up to 390 mum. In contrast, four of the pigs with vWd did not develop such lesions, two developed arteriosclerotic lesions affecting 6 and 7% of the aortic surface, and the seventh had 13% of the aortic surface involved. Most of the pigs with vWd, however, developed flat fatty lesions in contrast to the normal pigs whether on the normal or the high cholesterol diet. There was blue staining of the flat fatty lesions when two pigs with vWd were injected with Evans blue dye antemortem. By electron microscopy, severe endothelial damage was apparent, but there was no intimal proliferation. The coincidence of the impaired platelet-arterial wall interaction and lack of arteriosclerosis in this bleeding disease is discussed.

Inhibition of neutrophil lysosome-phagosome fusion associated with influenza virus infection in vitro. Role in depressed bactericidal activity.

The present study examined the effect of various unopsonized strains of influenza A virus on release of myeloperoxidase (MPO) and acid phosphatase in polymorphonuclear leukocytes (PMNL). These results were correlated with the effect that these same viruses had on bactericidal activity in PMNL. Several strains of virus inhibited the fusion of azurophil granules with phagosomes containing Staphylococcus aureus. These same strains inhibited the extracellular release of MPO from PMNL (39-59%) and caused depressed killing (42-77%). In contrast, one of the influenza viruses (X-47a) did not inhibit PMNL MPO release or killing. The data indicate a close relationship between the ability of influenza virus to ablate normal intracellular lysosome-phagosome fusion with subsequent depression of bactericidal functions of PMNL.

Increase in Platelet Factor 4-Like Activity in the Initial Stages of Atherosclerosis in Pigeons

The concept that platelets, by adhering to a damaged endothelial surface and releasing platelet factors, may play a role in the initiation of atherosclerosis has recently received further support by the group of Russell Ross and L.A. Harker (1). They have demonstrated that a heat stable, non-dializable low molecular weight protein released from platelets and detectable in serum may be implicated in the stimulation of the intimal cell proliferation at the initial stages of atherosclerosis. Because the known properties of this protein may be consistent with platelet factor 4, we decided to study the relationship between changes in platelet factor 4-like activity in serum and the development of atherosclerosis in two interesting species of pigeons: the white Carneau species that we call atherosclerosis-susceptible because they develop spontaneous atherosclerosis, first grossly apparent at 9 months of age and the show Racer species that we call atherosclerosis-resistant because they do not develop atherosclerosis.

Thrombocytes in atherosclerosis-resistant and atherosclerosis-susceptible breeds of pigeon: A comparative ultrastructural study

Abstract Thrombocytes from atherosclerosis-susceptible, White Carneau (WC), and atherosclerosis-resistant, Show Racer (SR), pigeons were studied using transmission and scanning electron microscopy. When fixed in phosphate-buffered glutaraldehyde, thrombocytes from WC and SR are oval to fusiform in shape and have eccentrically placed electron-dense nuclei, large electron-opaque organelles analogous to “dense bodies,” and extensively vacuolated cytoplasm. Ultrastructural studies following latex particle uptake and ruthenium red staining delineate two distinct cytoplasmic vacuole systems. One of the systems incorporates particles from the extracellular medium and the other is composed of vacuoles containing the electron-dense granules. Scanning EM reveals that SR thrombocytes adhere to and form aggregates on glass. In contrast, thrombocytes from WC pigeons with aortic lesions adhere less and do not form aggregates. These studies suggest that circulating thrombocytes from WC are altered during aortic lesion development.