David L. Haviland

Research Interests and Selected Publications

Research in my laboratory is directed in understanding the molecular mechanisms of inflammation. Phagocytic leukocytes are one of the body's first lines of defense against infection and the processes of inflammation direct the migration of polymorphonuclear neutrophils through the use of chemotactic factors. Such factors include the complement component C5a, Interleukin-8, and N-formyl peptides. Specifically, N-formyl peptides are derived from bacterial degradation and possibly from mitochondrial proteins upon tissue damage. In addition to chemotaxis, N-formyl peptides mediate many cellular and biochemical responses in activated neutrophils and macrophages, most notably, the generation of superoxide radicals, and proteolytic enzyme release from intracellular granules. If normal tissues are mis-identified, the activated neutrophil can mediate significant tissue destruction. The infiltration of neutrophils and macrophages into tissues are thought to play an important role in the pathogenesis of many diseases including adult respiratory distress syndrome [ARDS], inflammatory bowel disease, and rheumatoid arthritis. In these pathologies, it is thought that through the degradation of bacteria or breakdown of mitochondria, N-formyl peptides are generated which in turn sequester neutrophils. Work in our laboratory centers around the expression and regulation of the human N-formyl peptide receptor (fMLF-R). Although thought only to be expressed on myeloid cells, we have found the fMLF-R (as well as the C5a receptor) is expressed on non-myeloid cells such as liver parenchyma, cells of the central nervous system, and lung epithelium. What function and role in pathology the fMLF-R may play on these non-migrating tissues is unknown. This finding strongly suggests that the biological functions meditated by fMLF-R are likely to be more pleotropic and important than directing the migration of neutrophils. The goal of my laboratory is to examine the function, expression, genetics, and regulation of the human fMLF-R in non-myeloid cells, such as lung epithelium, and thereby better understand receptor's role during inflammation.

Selected Papers:

Wetsel, R.A., D.T. Fleischer, and D.L. HAVILAND. 1990. Deficiency of the Murine Fifth Complement Component (C5): A Two Base Pair Gene Deletion in a 5' Exon. J. Biol. Chem., 265:2435-2440.

HAVILAND, D.L., J.C. Haviland, D.T. Fleischer, A. Hunt, and R.A. Wetsel. 1991. Complete cDNA Sequence of Human Complement Pro-C5. Evidence of Truncated Transcripts Derived from a Single Copy Gene. J. Immunol., 146:362-368.

HAVILAND, D.L., J.C. Haviland, D.T. Fleischer, and R.A. Wetsel. 1991. Structure of the Murine Fifth Complement Component (C5) Gene. A Large Highly Interrupted Gene with a Variant Donor Splice Site and Organizational Homology with the Third and Fourth Complement Component Genes. J. Biol. Chem., 266:11818-11825.

Carney, D.F., D.L. HAVILAND, D. Noack, R.A. Wetsel, D.P. Vik, and B.F. Tack. 1991. Structural Aspects of the Human C5 Gene: Intron/Exon Organization, 5'-Flanking Region Features, and Characterization of Two Truncated cDNA Clones. J. Biol. Chem., 266:18786-18791.

HAVILAND, D.L., A.C. Borel, D.T. Fleischer, J.C. Haviland, and R.A. Wetsel. 1993. Structure, 5'-Flanking Sequence, and Chromosome Location of the Human N-Formyl Peptide Receptor Gene. A Single Copy Gene Comprised of Two Exons on Chromosome 19q13.3 that Yields Two Distinct Transcripts by Alternative Polyadenylation. Biochemistry, 32:4168-4174.

HAVILAND, D.L., R.L. McCoy, W.T. Whitehead, H. Akama, E.P. Molmenti, A. Brown, J.C. Haviland, W.C. Parks, D.H. Perlmutter, and R.A. Wetsel. 1995. Cellular Expression of the C5a Anaphylatoxin Receptor (C5a-R): Demonstration of C5a-R on Liver and Lung Cells. J. Immunol., 154:1861-1869.

Wang, X. D.T. Fleischer, W.T. Whitehead, D.L. HAVILAND, S.I. Rosenfeld, J.P Leddy, R. Snyderman, and R.A. Wetsel. 1995. Inherited Human Complement C5 Deficiency: nonsense Mutations in Exons 1 (Gln1 to Stop) and 36 (Arg1458 to Stop) and Compound Heterozygosity in Three African-American Families. J. Immunol., 154:5464-5471.

McCoy, R., D.L. HAVILAND, E.P. Molmenti, T. Ziambaras, R.A. Wetsel, and D.H. Perlmutter. 1995. The N-Formylpeptide and Complement C5a Receptors are Expressed in Liver Cells and Mediate Hepatic Acute Phase Gene Regulation. J. Exp. Med., 182:207-217.

Lacy, M., S.R. Whittemore, D.L. HAVILAND, R.A. Wetsel, and S.R. Barnum. 1995. Expression of the Receptors for the C5a Anaphylatoxin, Interleukin-8 and fMLP by Human Astrocytes and Microglia. J. Neuroimmunol., 61:71-78.

Hollmann,T.J., D.L. HAVILAND, J. Kildsgaard, K. Watts, and R.A. Wetsel. 1998. Cloning, expression, sequence determination, and chromosome localization of the mouse complement C3a anaphylatoxin receptor gene. Moleular Immunology 35: 137-148.


Back to David's main page...