Kenneth J. Longmuir
Professor, Physiology & Biophysics
School of Medicine
PH.D., University of Oregon, 1977
Phone: (949) 824-7257, 7781
Fax: (949) 824-8540
University of California, Irvine
C334, C310 Med Sci I
Mail Code: 4560
Irvine, CA 92697
Dr. Longmuir's primary area of interest is the interaction of liposomes with mammalian cells. A liposome is a microscopic, spherical structure composed of concentric bilayers of phospholipid. Medically useful compounds can K be entrapped within the aqueous spaces of the liposome for delivery into a cell. The laboratory is studying the mechanisms of uptake of liposomes by cells, and the subcellular distribution and subsequent metabolism of liposomal lipid after uptake. Several mechanisms of uptake are possible, such as fusion, endocytosis of the entire liposome, or transfer of individual lipids into the cell. Of particular interest in Dr. Longmuir's laboratory is the study of a family of synthetic peptides which, when incorporated into liposomes, promote rapid fusion of lipid bilayers. The intracellular transport of lipid is studied using fluorescently labelled lipids and confocal microscopy. Dr. Longmuir and colleagues have found that lipid head group composition significantly determines the path of intracellular transport. Also, some liposomal lipids are metabolized to products of lipid biosynthesis, whereas others are not. Such experiments address fundamental questions about how cells form membranes of different compositions for different parts of the cell.
A second area of interest in Dr. Longmuir's laboratory is the regulation, by cytokines, of cellular lipid metabolism. Inflammatory cytokines such as tumor necrosis factors and some of the interleukins stimulate eicosanoid biosynthesis (prostaglandins, leukotrienes, and thromboxanes) in a variety of cell types. Eicosanoids are important mediators of an inflammatory response, and many anti-inflammatory agents are in fact inhibitors of prostaglandin biosynthesis. Using biochemistry and molecular biology techniques, Dr. Longmuir's lab is studying the induction, by cytohnes, of enzyme actinties responsible for the rate-limiting steps of eicosanoid biosynthesis. In parallel with these studies of enzyme induction, the laboratory is using modern lipid biochemistry techniques to study cytokine regulation of cellular levels of free (non-esterified) arachidonic acid.the primary substrate for all eicosanoid biosynthesis. Particular emphasis is focused on the origin of the arachidonic acid. While mobilization of free arachidonic acid from intracellular membranes is a proven source of substrate in many experimental systems, data from Dr. Longmuir's experiments indicate that extra cellular stores of lipid (lipoproteins or fatty acid-albumin complexes) supply abundant quantities of arachidonic acid for cytohneinduced eicosanoid biosynthesis. Combining studies of enzyme induction with studies of substrate availability (rather than carrying out two separate investigations) should contribute significantly to our understanding of the regulation of cellular lipid metabolism by cytokines.
Longmuir, K.J. (1987) Biosynthesis and distribution of lipids. Curr. Topics Membranes and Transport 29: 129-174.
Longmuirj K.J. and L.A. Malinick. (1989) Transfer of phosphatidic acid from liposomes to cells is collision-dependent. Am. J. Physiol. 256: C522-C531.
Knauer, M.F., K.J. Longmuir, R.S. Yamamoto, T.P. Fitzgerald and G.A. Granger. (1990) Mechanism of human LT- and TNF- induced destruction of cells in vitro: Phospholipase activation and deacylation of a specific membrane phospholipid. J. Cell. Physiol 142: 469-479.
Ulich, T.R., K. Busser and K.J. Longmuir. (1990) Cytokine- and calcium ionophore A23187-mediated arachidonic acid metabolism in neutrophils. Cytokine 2: 280-286.