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Research Interests
Our approach has been to investigate immune responses of primitive deuterostomes,
the lineage of animals that includes sea urchins (echinoderms) and culminates
in mammals. Research efforts have focused on the immune cells, or coelomocytes
(phagocytic, macrophage-like cell found in the coelom) of the sea urchin
that become activated in response to injury or infection. Recently, we
have identified a number of genes that are expressed by activated coelomocytes,
some of which encode proteins that are likely to be involved in the immune
response. One is a homologue of the higher vertebrate complement component,
C3, which is the first protein in the alternate pathway. In mammals, the
activated fragment, C3b, binds directly to foreign cells. Another gene
expressed in coelomocytes is a homologue of factor B which is the second
protein in the alternate pathway. It binds to C3b, stabilizes it on foreign
cell surface and then together, they act within the enzyme cascade that
is the complement pathway. In the absence of immunoglobulins the sea urchin,
these two genes probably function to "identify" foreign cells
for subsequent removal and destruction by circulating phagocytic cell.
Evolutionarily, they may be little changed from the ancestral complement
genes in the ancestral deuterostome which may have given rise, through
gene duplication, to two sets of mammalian complement gene families. Through
the analysis of the sea urchin immune system, and through comparison to
immune systems in other deuterostomes, we aim to understand the evolutionary
changes that occurred in the immune responses of the lineage of animals
that lead to mammals.
Selected Publications Top
Smith, L.C.. Thioester function is conserved in SpC3, the sea urchin homologue of the complement component C3. submitted
Smith, L.C., L.A. Clow & D.P Terwilliger. 2001. The ancestral complement system in sea urchins. Immunological Reviews, 181:16-34.
Gross, P.S., L.A. Clow & L.C. Smith. 2000. SpC3, the complement homologue from the purple sea urchin, Strongylocentrotus purpuratus, is expressed in two subpopulations of the phagocytic coelomocytes. Immunogenetics, 51:1021-1033.
Clow, L.A., P.S. Gross, C.-S. Shih & L.C. Smith. 2000. Expression of SpC3, the sea urchin complement component, in response to lipopolysaccharide. Immunogenetics, 51:1043-1044.
Smith, L.C. 2001. The complement system in sea urchins. In Phylogenetic Perspectives on the Vertebrate Immune Systems (G. Beck, M. Sugumaran, E. Cooper, eds.). Plenum Publishing Co. pp. 363-372.
Smith, L.C., K. Azumi & M. Nonaka. 1999. Complement systems in invertebrates. The ancient alternative and lectin pathways. Immunopharmacology, 42:107-120.
Gross, P.S., W.Z. Al-Sharif, L.A. Clow & L.C. Smith. 1999. Echinoderm immunity and the evolution of the complement system. Developmental and Comparative Immunology, 23:429-442.
Smith, L.C., C.-S. Shih & S.G. Dachenhausen. 1998. Coelomocytes specifically express SpBf, a homologue of factor B, the second component in the sea urchin complement system. Journal of Immunology, 161:6784-6793.
Al-Sharif, W.Z., J.O. Sunyer, J.D. Lambris & L.C. Smith. 1998. A homologue of the complement component C3 is specifically expressed in sea urchin coelomocytes. Journal of Immunology, 160:2983-2997.
Smith, L.C., L. Chang, R.J. Britten & E.H. Davidson. 1996. Sea urchin genes expressed in activated coelomocytes are identified by expressed sequence tags (ESTs). Complement homologues and other putative immune response genes suggest immune system homology within the deuterostomes. Journal of Immunology, 156:593-602.
Smith, L.C., R.J. Britten & E.H. Davidson. 1995. Lipopolysaccharide activates the sea urchin immune system. Developmental and Comparative Immunology, 19:217-224.
Smith, L.C., M.G. Harrington, R.J. Britten & E.H. Davidson. 1994. The sea urchin profilin gene is expressed in mesenchyme cells during gastrulation. Developmental Biology, 164:463-474.
Smith, L.C. & E.H. Davidson. 1994. The echinoderm immune system: characters shared with vertebrate immune systems, and characters arising later in deuterostome phylogeny. In: Primordial Immunity: Foundations for the Vertebrate Immune System. (G. Beck, E. L. Cooper, G. S. Habicht and J. J. Marchalonis, eds.) The New York Academy of Sciences, 712:213-226.
Smith, L.C. & E.H. Davidson. 1992. The echinoid immune system and
the phylogenetic occurrence of immune mechanisms in deuterostomes. Immunologytoday
13:356-362.
(The echinoid immune system revisited: reply. Immunologytoday, 14:93-94.)
Smith, L.C., R.J. Britten & E.H. Davidson. 1992. SpCoel1, a sea urchin profilin gene expressed specifically in coelomocytes in response to injury. Molecular Biology of the Cell, 3:403-414.
For copies of my papers on immune functions
in marine sponges, please email me.
Contact Information Top
Department of Biological Sciences
George Washington University
334 Lisner Hall, 2023 G Street. NW
Washington, D.C. 20052
Office: 202-994-9211, Fax: 202-994-6100
email: csmith@gwu.edu
see also: www.gwu.edu/%7Eclade/faculty/smith/
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