Holly H. Birdsall, M.D., Ph.D. - Faculty
Professor, Departments of Otolaryngology and Pathology & Immunology
Medical School: Baylor College of Medicine (M.D./Ph.D.)
Residency: Baylor College of Medicine
M.P.H.: University of Texas-Houston, School of Public Health
Research Interests: Transendothelial Migration of Leukocytes in Inflammation; AIDS Dementia; Ischemia; Virus:leukocyte interactions
Our goal is to identify mechanisms influencing the translocation of mononuclear leukocytes (MNLs) across vascular endothelial barriers in the context of viral infections like HIV. Over 40 percent of HIV-infected patients develop dementia. HIV-1 in the CNS is found primarily amidst perivascular leukocytic infiltrates which are a potential source of diverse products that contribute to neurologic dysfunction. Our hypothesis is that the activation of MNLs in association with HIV-1 infection increases their ability to migrate across vascular endothelium and produce factors that stimulate additional MNLs to migrate across the same vascular endothelium. We use a model of cultured umbilical vein and brain microvascular endothelium grown over collagen to study the adhesive and transendothelial migratory behavior of MNLs. HIV-infected MNLs are obtained from the peripheral blood of from HIV-infected patients or by infecting normal donor MNLs with HIV in vitro. Flow cytometric analyses identify and classify the MNLs that migrate through the endothelial barrier and are also used to measure cytokine production by these migratory MNLs. We have demonstrated that HIV-1 infection stimulates expression of specific integrins and other yet uncharacterized cell surface molecules that facilitate adhesive interactions with both endothelium and cultured neural cells. In a subset of HIV-infected subjects, we observed that significantly increased numbers of T lymphocytes spontaneously migrate across these endothelial monolayers in comparison with MNLs from normal donors. These migratory lymphocytes appear to be able to enhance subsequent migration of additional leukocytes into the same perivascular focus.
Wang F. Trial J. Diwan A. Gao F. Birdsall HH. Entman ML. Hornsby PJ. Siasurbramaniam N. Mann DL. Regulation of cardiac fibroblast cellular function by leukemia inhibitory factor. Journal of Molecular Cell Cardiology 34:1309-1316, 2002.
Birdsall HH. Siwak EB, Trial J. Rodriguez-Barradas M. White AC Jr. Wietgrefe S. Rossen RD. Transendothelial migration of leukocytes carrying infectious HIV-1: An indicator of adverse prognosis. AIDS 16(1):5-12, 2002.
Trial J. Baughn RE. Wygant JN. McIntyre BW. Birdsall HH. Youker KA. Evans A. Entman ML. Rossen RD. Fibronectin fragments modulate monocyte VLA-5 expression and monocyte migration. Journal of Clinical Investigation. 104(4):419-430, 1999.
Birdsall HH. Trial J. Lin HJ. Green DM. Sorrentino GW. Siwak EB. de Jong AL. Rossen RD. Transendothelial migration of lymphocytes from HIV-1 infected donors: A mechanism for extravascular dissemination of HIV-1. Journal of Immunology. 158(2):5968-5977, 1997.
Youker KA. Birdsall HH. Frangogiannis NG. Kumar AG. Lindsey ML. Ballantyne CM. Rossen RD. Entman ML. Phagocytes in ischemic injury. In Phagocytes: Biology, Physiology, Pathology, and Pharmacotherapeutics. Annuals of the New York Academy of Sciences. 832:243-265, 1997.
Green DM. Trial J. Birdsall HH. TNF-a released by co-migrating monocytes promotes transendothelial migration of activated lymphocytes. Journal of Immunology. 161:2481-2489, 1997.
Kumar AG. Ballantyne CM. Michael LH. Kukielka GL. Youker KA. Lindsey ML. Hawkins HK. Birdsall HH. MacKay CR. LaRosa GJ. Rossen RD. Smith CW. Entman ML. Induction of monocyte chemoattractant protein-1 in the small veins of the ischemic and reperfused canine myocardium. Circulation. 95(3):693-700, 1997.
Birdsall HH. Green DM. Trial J. Youker KA. Burns AR. MacKay CR. LaRosa GJ. Hawkins HK. Smith CW. Michael LH. Entman ML. Rossen RD. Complement C5a, TGF-beta 1, and MCP-1, in sequence, induce migration of monocytes into ischemic canine myocardium within the first one to five hours after reperfusion. Circulation. 95(3):684-92, 1997.
de Jong AL. Green DM. Trial JA. Birdsall HH. Focal effects of mononuclear leukocyte transendothelial migration: TNF-alpha production by migrating monocytes promotes subsequent migration of lymphocytes. Journal of Leukocyte Biology. 60(1):129-36, 1996.
Kapadia S. Lee J. Torre-Amione G. Birdsall HH. Ma TS. Mann DL. Tumor necrosis factor-alpha gene and protein expression in adult feline myocardium after endotoxin administration. Journal of Clinical Investigation. 96(2):1042-52, 1995.
To see a complete listing of Dr. Birdsall's publications, visit PubMed.