The major research interests of our group have been the function of platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) in reproductive biology including ovulation, sperm activation, implantation, autoimmunity, fetal lung maturation and parturition. The PAF content of the rat uterus increased 4-fold during the latter stage of pregnancy. In contrast, the placenta PAF content decreased. The changes can be accounted for by the change in PAF-acetylhydrolase (-AH) activity, the enzyme that inactivates PAF in these tissues. The decreased concentration in the in the placenta and the increase in uterus may contribute to the fetoplacental circulation as well as the delivery of the placenta only after fetal expulsion. We have recently established a role for PAF in sperm activation. It was demonstrated that mRNA for the PAF-AH found in epididymal fluid is present in the epididymal epithelium and the activity of the enzyme in epididymal fluid is 30 times higher than that found in plasma. The PAF-AH activity present in semen has been suggested to occupy a central role in fertilization. A role for PAF in necrotizing enterocolitis (NEC) has been established. The development of this disease can be prevented by increasing the plasma PAF-AH activity by the administration of dexamethasone. PAF-AH has been demonstrated in human milk. It is suggested that PAF-AH activity in milk may explain, in part, the decreased incidence of NEC in newborns that are breast fed. The intestine of the newborn rat has a high capacity for PAF biosynthesis. This observation may explain, in part, the reason why the small bowel is very susceptible to necrosis. The prevention of NEC can also be prevented by the pretreatment of rats with recombinant PAF-AH.
RESEARCH INTERESTS
Platelet-activating factor (PAF)
Role of PAF in reproduction and development including sperm motility, ovulation, fertilization,implantation, fetal lung maturation, and parturition
PAF in the development of necrotizing enterocolitis of the newborn and its role in age related macular degeneration
Molecular mechanisms of macular degeneration
RECENT PUBLICATIONS
Kawano, Y. , Narahara, H., and Johnston, J.M., "Inhibitory effect of interleukin-8 on the secretion of platelet-activating factor acetylhydrolase by human decidual macrophages." J Soc Gyn Invest, 6:328-332, 1999
Marques, M., Pei, Y., Southall, M.D., Johnston, J.M., Arai, H., Aoki, J., Inoue, T., Seltmann, H., Zouboulis, C.C., Travers, J.B., Narahara, H., Mine, S-C., and Kawano, Y., "Identification of platelet-activating factor acetylhydrolase II in human skin." J Invest Dermatol, 119:913-919, 2002
Narahara H, s-c Mine, Y Kawano. JM Johnston, "Effect of Colony-Stimulating Factors on the Secretion of Platelet-Activating Factor by Decidual Macrophages." Obstet Gynecol., 188:157-161, 2003
Narahara H,Y Kawano,K Nasu, J Yoshimatsu, JM Johnston, I Miyakawa, "Platelet-Activating Factor Inhibits the Secretion of Platelet-Activating Factor Acetylhydrolase by Human Decidual Macrophages." J Clin Endocrinol Metab., 88:6029-6033, 2003
Narahara, J., and Johnston, J.M., "Role of PAF in cervical softing and sperm motility." In Press,
SIGNIFICANT PUBLICATIONS
Muguruma K, Furukawa M, Tjoelker LW, Dietsch G, Gray PW, Zhao B, Johnston JM., "Prevention of necrotizing enterocolitis. The role of platelet-activating factor acetylhydrolase." Adv Exp Med Biol, 416:129-133, 1996
Muguruma K, JM Johnston, "Metabolism of platelet-activating factor in rat epididymal spermatozoa." Biol Reprod, 56:529-536, 1997
Matsubara T, K Yasuda, JM Johnston, M Sanezumi, H Okada, S Matsuoka, H Kanzaki, "Platelet-activating factor and platelet-activating factor acetylhydrolase activity in rat uterus and placenta during the latter stages of pregnancy." Biol Reprod, 56:885-890, 1997
Guerra R, B Zhao, V Mooser, D Stafforini, JM Johnston, JC Cohen, "Determinants of platelet-activating factor acetylhydrolase: Heritability and relationship to plasma lipoproteins." J Lipid Res, 38:2281-2288, 1997
Narahara H, I Miyakawa, JM Johnston, "Platelet-activating factor in human decidua: Its role in parturition and preterm labor." Trophoblast Res, 9:99-107, 1997
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