Docosahexaenoic acid (DHA) alters the phospholipid molecular species composition of membranous vesicles exfoliated from the surface of a murine leukemia cell line.

Previously, we presented evidence that the vesicles routinely exfoliated from the surface of T27A tumor cells arise from vesicle-forming regions of the plasma membrane and possess a set of lateral microdomains distinct from those of the plasma membrane as a whole. We also showed that docosahexaenoic acid (DHA, or 22:6n-3), a fatty acyl chain known to alter microdomain structure in model membranes, also alters the structure and composition of exfoliated vesicles, implying a DHA-induced change in microdomain structure on the cell surface. In this report we show that enrichment of the cells with DHA reverses some of the characteristic differences in composition between the parent plasma membrane and shed microdomain vesicles, but does not alter their phospholipid class composition. In untreated cells, DHA-containing species were found to be a much greater proportion of the total phosphatidylethanolamine (PE) pool than the total phosphatidylcholine (PC) pool in both the plasma membrane and the shed vesicles. After DHA treatment, the proportion of DHA-containing species in the PE and PC pools of the plasma membrane were elevated, and unlike in untreated cells, their proportions were equal in the two pools. In the vesicles shed from DHA-loaded cells, the proportion of DHA-containing species of PE was the same as in the plasma membrane. However, the proportion of DHA-containing species of PC in the vesicles (0.089) was much lower than that found in the plasma membrane (0.194), and was relatively devoid of species with 16-carbon acyl components. These data suggested that DHA-containing species of PC, particularly those having a 16-carbon chain in the sn-1 position, were preferentially retained in the plasma membrane. The data can be interpreted as indicating that DHA induces a restructuring of lateral microdomains on the surface of living cells similar to that predicted by its behavior in model membranes.

An outbreak of infection by Yersinia pseudotuberculosis in nonhuman primates.

Between October 1970 and June 1971, at the National Center for Primate Biology, Yersinia pseudotuberculosis of serotypes I-B and III was isolated from 9 monkeys (one during life and 8 at necropsy) of the following species: Macaca cynomolgus, Macaca nemestrina, Macaca radiata and Cercocebus fulliginosus. All these animals had characteristic gastrointestinal lesions consisting of superficial erosions or ulcerations with masses of gram-negative coccobacilli and an acute inflammatory exudate. Involvement of mesenteric nodes, livers and spleens by similar lesions was common. A more granulomatous reaction was rarely seen. Similar lesions without bacteriologic confirmation were found at necropsy in 20 other animals. When guinea pigs were inoculated intraperitoneally with our isolates, they developed focal splenic and hepatic necrosis resembling the septicemic form of the disease which is seen rarely in man. When inoculated intraperitoneally, they developed mesenteric lymphadenitis resembling human nonspecific mesenteric lymphadenitis; no intestinal lesions could be detected in the animals inoculated orally. The granulomatous component of the inflammatory response was better developed in guinea pigs than in the monkeys. It is concluded that infection by Yersinia pseudotuberculosis in nonhuman primates and probably also in other species, including man, is primarily a gastrointestinal disease. The primary intestinal lesions may be conspicuous, as in the monkeys, or inconspicuous, as in the guinea pig and man. The acuteness of the inflammatory response in the monkeys, when compared to the more granulomatous reaction in guinea pigs, suggests that the great majority of the monkeys died from an overwhelming infection before they could develop hypersensitivity to the organism.

Respiratory pathogens in monkeys.

Respiratory disease in a dynamic colony of nonhuman primates during a 4-year period was due primarily to infections caused by Klebsiella pneumoniae, Diplococcus pneumoniae, Bordetella bronchiseptica, Pasteurella multocida, and Haemophilus influenzae. The principal secondary invaders were Escherichia coli, Staphylococcus aureus, and streptococci. A high fatality rate was associated with infections caused by each of the primary pathogens, and females appeared to be more susceptible than males. Incidence of respiratory disease was greatest in the fall and early winter; however, at all times newly colonized monkeys had a higher infection rate than conditioned monkeys. Infections were occasionally confined only to the lungs and were sometimes present without grossly observable lung lesions. The information given on susceptibility of 10 species of nonhuman primates to respiratory infections provides a basis for developing disease models.

Enteric pathogens in monkeys.

From 1964 to 1967, 6,646 monkeys, representing 10 primate species, were examined for Shigella and Salmonella infections upon arrival at the National Center for Primate Biology. Of these animals, 12% were infected with Shigella, and 75% of the Shigella isolates were S. flexneri 4. The incidence of Salmonella infections decreased from 12 to 3% during the period of study. Epidemiological studies of animals in the colony for 90 days or more indicated no seasonal variation in the occurrence of Shigella and Salmonella. Many of the isolates from incoming monkeys as well as from laboratory-conditioned animals were resistant to chloramphenicol, dihydrostreptomycin, and tetracycline. The possible operation of drug-resistance factors in these infections is discussed.