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Guy A. Cabral , Ph.D.
Professor/Chair of the Graduate Program Committee
Phone: (804) 828-2306
Dept. Fax: (804) 828-9946
e-mail: gacabral@vcu.edu
Address:
Department of Microbiology & Immunology
Virginia Commonwealth University
PO Box 980678
1101 E. Marshall St., 7-065 Sanger Hall
Richmond, VA 23298-0678
Professional Experience
- B.S.,
1967, University of Massachusetts
- M.S.,
1970, University of Connecticut
- Ph.D.,
1974, University of Connecticut
-
Postdoctoral, 1974-1976, Baylor College of Medicine
Research Interests:
The goal of this research is to define the effect of
Delta-9-tetrahydrocannabinol (THC), the major psychoactive component of
marijuana, on macrophage antigen presentation. We have shown that THC alters
antigen presentation by exerting differential effects on macrophage
processing of antigens via the endosomal pathway. The outcome of THC effects
was dependent on the conformation of the antigen. In the present study, we
will test the hypothesis that THC alters macrophage functional competence,
at least in part, by influencing a subset of steps during antigen processing
whose role is dictated by the structure of the antigen. First, we will
determine the effect of THC on the processing of antigens ingested via the
phagosomal pathway to determine whether THC affects this alternative
pathway. The effect of THC on this antigen processing will be established
using Bacillus subtilis as a degradative marker and a viability
bacterial colony count recovery assay. Second, we will examine the effect of
THC on three major aspects of antigen processing, including disruption of
disulfide bonds in an antigen, enzymatic activity of acid proteases called
cathepsins, and status of the intracellular reducing environment. Third, we
will define the effect of THC on the co-localization of molecules involved
in antigen processing and presentation. Immunoelectron microscopy will
employ cross-linked 15-nm gold-labeled globulins as a tracer for antigen
processing and 5-nm gold-labeled monoclonal MK-D6 anti-Ia antibody as a
tracer for Class II molecules. Fourth, we will define the role of a
cannabinoid receptor in altering antigen processing. Functional assessment
of a role of a cannabinoid receptor in mediating antigen processing will be
achieved using pertussis toxin uncoupling, reconstitution with t2cAMP, CB1
selective antagonism with SR141716A, and structural activity relationships
for demonstrating stereoselectivity for the enantiomeric pairs
(-)CP55940/(+)CP56667 and (-)HU210/(+)HU211. Implication of a functional
cannabinoid receptor in mediating antigen processing will be followed by
characterization of receptor protein expression using anti-cannabinoid
receptor subtype antibodies to CB1, CB1a, and CB2 in Flow Cytometry and
ELISA and detection of receptor subtype-specific mRNA by Mutagenic Reverse
Transcription Polymerase Chain Reaction to relate receptor differential
expression to macrophage activation state.
Selected Publications:
1. McCoy, K.L.,
Gainey, D., and Cabral, G.A. Delta-9-tetrahydrocannabinol modulates antigen
processing by macrophages. J. Pharmacol. Exptl. Ther, 273:1216-1223,
1995.
2. Burnette-Curley,
D., and Cabral, G.A. Differential inhibition of macrophage tumoricidal
activity by delta-9-tetrahydrocannabinol. Proc. Soc. Exptl. Biol. Med,
210:64-76, 1995.
3. Clements, D.J.,
Cabral, G.A., and McCoy, K.L. Delta-9-tetrahydrocannabinol selectively
inhibits macrophage costimulatory activity and down regulates heat-stable
antigen expression. J. Pharmacol. Exptl. Ther. 277:1315-1321, 1996.
4. Specter, S., and
Cabral, G. A. Cannabinoids, Immunity and Resistance to Infections. J.
Neuroimmunol. 69:15-23, 1996.
5. Sakai, K., Long,
S.D., Dove Pettit, D.A, Cabral, G.A., and Schwartz, L. B. Expression of a
recombinant human tryptase in a baculovirus system. Protein Expression and
Purification, 7:67-73, 1996.
6. Dove Pettit,
D.A., Williamson, J., Cabral, G.A., and Marciano-Cabral, F. In vitro
destruction of nerve cell cultures by Acanthamoeba: A transmission and
scanning electron microscopy study. J. Parasitol. 82(5): 769-777,
1996.
7. Nowell, K. W.,
Dove Pettit, D. A., Cabral, W. A., Zimmerman, H. W., Jr., Abood, M. E., and
Cabral, G. A. High level expression of the human CB2 cannabinoid receptor
using a baculovirus system. J. Biochem. Pharmacol. 55:1893-1905,
1998.
8. Cabral, G.A.,
and Dove Pettit, D. Drugs and Immunity: Cannabinoids and their role in
decreased resistance to infectious disease. J. Neuroimmunol., 83:
116-123, 1998.
9. Dove Pettit, D.,
Harrison, M. P., Spencer, R. F., and Cabral, G.A. Immunohistochemical
localization of the neural cannabinoid receptor in rat brain. J. Neurosci.
Res., 51:391-402, 1998.
10. Waksman, Y.,
Olson, J., Boothe, C., and G. A. Cabral. Cannabinoids inhibit nitric oxide
release from activated rat microglial cells. J. Pharmacol. Exptl. Ther.,
288:1357-1366, 1999.
11. McCoy, K. L.,
Clements, D. J., Carlisle, S. J., and Cabral, G. A. Evidence for CB2
receptor participation in inhibition of macrophage antigen processing. J.
Pharmacol. Exptl. Ther. 289:1620-1625, 1999.
12. Tao, Q.,
McAllister, S. D., Andreassi, J., Nowell, K. W., Cabral, G. A., Hurst, D.
P., Reggio, P. H., and Abood, M. E. Role of a conserved lysine residue in
the CB2 cannabinoid receptor: Evidence for subtype specificity. J. Mol.
Pharmacol.55:605-613, 1999.
13. Marciano-Cabral,
F., Puffenbarger, R., and Cabral, G. A. The increasing importance of
Acanthamoeba infections. J. Eukaryotic Microbiol. 47(1): 29-36,
2000.
14. Puffenbarger, R.
A., Boothe, A. C., and Cabral, G.A. Cannabinoids inhibit differentially
cytokine gene expression in rat microglial cells. Glia, 29:58-69,
2000.
15. Matveyeva, M.,
Hartmann, C. B., Harrison, T. M., Cabral, G. A., and McCoy, K. L.
Delta-9-tetrahydrocannabinol selectively increases aspartyl cathepsin D
proteolytic activity and impairs lysozyme processing by macrophages. Int. J.
Immmunopharmacol., 22: 373-381, 2000.
16. Marciano-Cabral,
F.,Ferguson, T., Gaylen Bradley,S., and Cabral, G.
Delta-9-tetrahydrocannabinol (THC), the major psychoactive component of
marijuana, exacerbates brain infection by Acanthamoeba. J. Eukar.
Microbiol.,48: 4S-5S, 2001.
17. McAllister, S. D.,
Tao, Q., Barnett-Norris, J., Buehner, K., Hurst, D. P., Guarnieri, F.,
Reggio, P. H., Nowell Harmon, K. W., Cabral, G. A., and Abood, M. E. A
critical role for a Tyrosine residue in the cannabinoid receptors for ligand
recognition and signal transduction. Biochem. Pharmacol. 63:2121-2136,
2002.
18. Carlisle, S. J.,
Marciano‑Cabral, F., Staab, A., Ludwick, C., and Cabral, G. A. Differential
expression of the CB2 cannabinoid receptor by rodent macrophages and
macrophage‑like cells in relation to cell activation. Biochem. Pharmacol.,
2:69-82, 2002.
19. Howlett, A. C.,
Barth, F., Bonner, T. I., Cabral, G., Casellas, P., Devane, W.A., Felder,
C.C., Herkenham, M., Mackie, K., Martin, B.R., Mechoulam R., and Pertwee,
R., R.G. International Union of Pharmacology XXVII.Classification of
cannabinoid receptors.
Pharmacol.
Rev. 54: 161-202, 2002.
20.
Marciano-Cabral, F., and Cabral, G.A. Acanthamoeba spp.
As agents of disease in
humans. Clin Microbiol. Rev. 16:273-307, 2003.
21. Olson, J.M.,
Kennedy, S.J., and Cabral, G.A. Expression of the murine CB2 cannabinoid
receptor using a recombinant Semliki Forest virus. Biochem. Pharmacol. 65:1931-1942,
2003.
22. Marciano-Cabral,
Han, K., Powell, E., Ferguson, T., and Cabral, G. Interaction of an
Acanthamoeba human isolate harboring bacteria with murine peritoneal
macrophages. J. Eukaryot. Microbiol. 50: 516-519, 2003.
23. Peterson, P.K.,
Gekker, G., Hu, S., Cabral, G., and Lokensgard, J.R. Cannabinoids and
morphine differentially affect HIV-1 expression in CD4+ lymphocyte and
microglial cell cultures. J. Neuroimmunol. 147: 123-126, 2004.
24. Cabral, G.A.
Cannabinoid-mediated exacerbation of brain infection by opportunistic amebae.
J. Neuroimmunol. 147:127-130, 2004.
25. Marciano-Cabral,
F., Ludwick, C., Puffenbarger, R. A., and Cabral, G. A. Differential
stimulation of microglial pro-inflammatory cytokines by Acanthamoeba
culbertsoni versus Acanthamoeba castellanii. J. Eukaryot.
Microbiol. 51(4): 472-479, 2004.
26. Peterson, P.K.,
Gekker, G., Hu, S., Cabral, G., and Lokensgard, J.R. Cannabinoids and
morphine differentially affect HIV-1 expression in CD4+ lymphocyte and
microglial cell cultures. J. Neuroimmunol. 147: 123-126, 2004.
27. Cabral, G.A.
Cannabinoid-mediated exacerbation of brain infection by opportunistic amebae.
J. Neuroimmunol. 147:127-130, 2004.
28. Marciano-Cabral,
F., Ludwick, C., Puffenbarger, R. A., and Cabral, G. A. Differential
stimulation of microglial pro-inflammatory cytokines by Acanthamoeba
culbertsoni versus Acanthamoeba castellanii. J. Eukaryot.
Microbiol. 51(4): 472-479, 2004.
29. Sheng, W. S., Hu,
S., Min, X., Cabral, G. A., Lokensgard, J. R., and Peterson, P. K. Synthetic
cannabinoid WIN55,212-2 inhibits generation of inflammatory mediators by
IL-1β-stimulated human astrocytes. Glia 49:211-219, 2005.
30. Cabral, G. A.
Lipids as bioeffectors in the immune system. Life Sciences 77:1699-1710,
2005.
31. Cabral, G. A.,
and Marciano-Cabral, F. Cannabinoids and susceptibility to neurological
infection by free-living amebae. In: Friedman, H., Klein, T. W., and
Bendinelli, M. (eds). Infectious Agents and Pathogenesis: Infectious
Diseases and Substance Abuse. Springer Science, New York. pp. 51-65,
2005.
32. Cabral, G. A.,
and Marciano-Cabral, F. Cannabinoid receptors in microglia of the central
nervous system: Immune functional relevance. J. Leuk. Biol. 78:1192-1197,
2005.
33. Cabral, G. A.
Localization of cannabinoid receptors using immunoperoxidase methods. In:
Onaivi, E. S. (ed). Methods in Molecular Medicine: Marijuana and
Cannabinoid Research: Methods and Protocols. Humana Press, Inc. Totowa,
NJ. pp. 41-69, 2005.
34. Cabral, G. A.,
and Staab, A. Effects on the immune system. In: Pertwee, R. (ed).
Handbook on Experimental Pharmacology: Cannabinoids. Springer-Verlag,
Berlin. 168:385-423, 2005.
35. Klein, T. W., and
Cabral, G. A. Cannabinoid-induced immune suppression and modulation of
antigen-presenting cells. J. Neuroimmun. Pharmacol. 1:50-64, 2006.
36. Marciano-Cabral,
F., Raborn, E. S., Martin, B. R., and Cabral, G. A.
Delta-9-tetrahydrocannabinol, the major psychoactive component in marijuana,
inhibits macrophage chemotaxis to Acanthamoeba. J. Eukaryot.
Microbiol. 53(S1): S15-S17, 2006.
37. Cabral, Guy A.
Drugs of abuse, Immune Modulation, and AIDS. J. Neuroimmun. Pharmacol. 1:280-295,
2006.
38. Rocha-Azevedo,
B., Jamerson, M., Cabral, G. A., Silva-Filho, F. C., and Marciano-Cabral, F.
The interaction between the amoeba Balamuthia mandrillaris and
extracellular matrix glycoproteins in vitro. Parasitology. 134:51-58,
2007.
39. Rock, R.B.,
Gekker, G., Hu, S., Sheng, W.S., Cabral, G.A., Martin, B.R., and Peterson,
P.K. WIN55,212-2-mediated inhibition of HIV-1 expression in microglial
cells: Involvement of cannabinoid receptors. J. Neuroimmune Pharmacol. 2:178-183,
2007.
40. Raborn, E.S.,
Marciano-Cabral, F., Buckley, N.E., Martin, B.R., and Cabral, G.A. The
cannabinoid delta-9-tetrahydrocannabinol mediates inhibition of macrophage
chemotaxis to RANTES/CCL5: Linkage to the CB2 receptor. J.
Neuroimmune Pharmacol., In press.
41. Cabral, G.A.,
Raborn, E.S., Griffin, L., Dennis, J., and Marciano-Cabral, F. CB2 receptors
in the brain: role in central immune function. Br. J. Pharmacol. 2:178-183,
2007.
42. Marciano-Cabral,
F., and Cabral, G. The immune response to Naegleria fowleri amebae
and pathogenesis of infection. FEMS Immunol. Med. Microbiol. 51:
243-259, 2007. |
