 Degrees and Certifications:
PhD Rank and Title:
Associate Chairman Department:
Immunology/Microbiology Endowed Professorship:
Office Location:
1735 W. Harrison St.
Cohn Building
Room 636
Chicago, IL 60612 Laboratory Location:
1735 W. Harrison Street
Room 636A Cohn Building
Chicago, IL, 60612 Phone:
312-942-3518 Fax:
312-942-2808 E-mail:
lthomas2@rush.edu
Education:
BA, 1968, Beloit College
PhD, 1973, University of Chicago Medical Center
Research Areas:
Biological Phenomena Cell Phenomena and Immunity
Immune System Diseases
Respiratory Tract Diseases
Laboratory Techniques:
Cytokine Assessment
Flow Cytometry
Tissue Culture (Primary, Cell Line)
Western Northern Southern Blotting
Hyperlinks:
Documents:
Faculty/Staff Description:
The laboratory has two major projects. One project is investigating the roles that neutrophils may play in asthma. Chronic asthma is an inflammatory disease characterized by airway hyper-responsiveness, infiltration of CD4 lymphocytes and eosinophils, and airway remodeling. Severe asthma, which is manifest as frequent exacerbations of chronic asthma or as persistent, steroid-resistant asthma, is a major cause of morbidity and mortality in asthma. Neutrophils are implicated in the pathogenesis of severe asthma, both in acute exacerbations of chronic asthma and in the steroid-resistant form of asthma. In this context, my laboratory has studied mechanisms for an interaction between neutrophils and eosinophils in asthma. We have demonstrated that major basic protein (MBP), which is released specifically by eosinophils and is also implicated in the pathogenesis of asthma, activates several of the neutrophil inflammatory functions, including production of reactive oxygen products, degranulation, and cytokine production. We also demonstrated, conversely, that lactoferrin, which is uniquely synthesized by neutrophils and glandular epithelial cells, activates several of the eosinophil inflammatory functions, including degranulation, when immobilized on a surface. Together, these findings demonstrate a potential for the cross-mutual activation of eosinophils and neutrophils in asthma and suggest a mechanism by which an influx of neutrophils that is superimposed on the chronic influx of eosinophils in an asthmatic airway can exacerbate chronic asthma. A goal of this project is to define the receptor mechanisms that mediate the reciprocal activation of neutrophils and eosinophils, with a long term goal being the development of specific antagonists for therapeutic testing.
The second project in the laboratory is investigating the role that neutrophils may play in HIV-1 disease. It had been reported previously that neutrophils bind HIV-1 and that neutrophil-bound HIV-1 is more efficient that free HIV-1 in the infection of CD4+ lymphocytes. The mucosa is the portal of entry for both sexual and vertical mother-to-child transmission of HIV-1 infection, and neutrophils are present along the mucosa and accumulate further in response to mucosal infection. Together, these finding suggest that neutrophils may contribute to HIV-1 infection and transmission, particularly to the increased risk of HIV-1 transmission associated with mucosal inflammation. We have demonstrated that activation of the neutrophils by pro-inflammatory molecules such as TNF-a increases neutrophil binding of HIV-1 and also accelerates infection of the lymphocytes by the neutrophil-bound HIV-1. These findings suggest neutrophils in semen of HIV-1-infected men or in breast milk of HIV-1 infected women may act as carriers for the transmission of HIV-1 infection. Similarly, neutrophils present in the mucosa of the female genital tract could bind free HIV-1 and facilitate the transfer of virus to CD4+ lymphocytes present in the mucosa. Of additional interest, findings by our laboratory indicate that HIV-1 can cause a non-productive infection in neutrophils that is characterized by synthesis of early viral proteins critical to HIV-1 infection. The goals of this project are to identify the mechanisms and clinical significance for HIV-1 binding by neutrophils and for the capacity of neutrophil-bound HIV-1 to productively infect lymphocytes and to non-productively infect neutrophils.
Selected Publications:
Thomas, L.L., W. Xu, and T.T. Ardon. 2002. Immobilized lactoferrin is a stimulus for eosinophil activation. J. Immunol. 169: 993-999.
Morgan, D., V.V. Cherny, W. Xu, L.L. Thomas, and T.E. DeCoursey. 2003. Temperature dependence of NADPH oxidase and its related H+ channel in human eosinophils. J. Physiol. 550:447-458
Shenoy, N., G.J. Gleich, and L.L. Thomas. 2003. Eosinophil granule major basic protein stimulates neutrophil superoxide production by a class IA phosphoinositide 3-kinase and protein kinase C-z dependent pathway. J. Immunol. 171:3734-3741.
Gabali, A.M., J. Anzinger, G.S. Spear, and L.L. Thomas. 2004. Activation by inflammatory stimuli increases neutrophil binding of HIV-1 and subsequent infection of lymphocytes by the bound virus. J. Virol. 78: 10833-10836.
Anzinger, J, A.M. Gabali, L.L. Thomas, and G.T. Spear. Efficient HIV Infection of Peripheral Blood Mononuclear Cells Requires a Cell-Surface Ca2+-Dependent Molecular Interaction. Submitted for publication.
Gabali, A.M., X. Ji, , G.T. Spear, and L.L. Thomas. HIV-1 causes a non-productive infection in neutrophils. Manuscript in preparation.
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