C. Wayne Smith, M.D.
Professor, Departments of Pediatrics and Immunology
M.D., The University of Texas Medical Branch at Galveston
Postdoctoral, The University of Texas Medical Branch at Galveston
Mechanisms of Leukocyte Accumulation in Inflammation and Tissue Injury
Dr. Smith's research focuses on inflammation and wound healing, the mechanisms of leukocyte accumulation at sites of inflammation and tissue injury, and the influence of dietary factors on these processes. Specific molecular mechanisms are analyzed in vitro with isolated leukocytes and endothelial monolayers in flow chambers that simulate some aspects of blood flow in post-capillary venules. Here we assess adhesion, transendothelial migration, and the phenotypic changes leukocytes undergo during and after the process of transendothelial migration. Application of these insights to physiology in vivo involves mouse models of inflammation. A model of ocular surface injury (simple corneal abrasion) is used to induce an inflammatory response to injury. Intravital microscopy allows direct visualization in real time of the inflammatory events in the cornea and in other vascular beds that are directly accessible to observation. The use of knockout and transgenic mice, blocking monoclonal antibodies, and targeted inhibition allow analysis of molecular mechanisms.
His studies of the influence of dietary factors on the inflammatory process are currently limited to the effects of high fat diets in murine models. Using insights from the basic research on inflammation, we analyze cytokines, chemokines, leukocyte changes, adhesion molecules, toll-like receptors and injury in tissues of mice fed ad lib. diets high in either milk fat (“Western diet”) or corn oil and high sucrose. These studies currently focus on the inflammatory and anti-inflammatory changes in adipose tissues, liver, blood, and corneal wound responses. We are analyzing the increases in number and subtypes of macrophages, lymphocytes, neutrophils and platelets, their phenotypic changes as obesity progresses, and the changes in inflammatory mediators (e.g, chemokines and cytokines) and inhibitors (e.g., anti-inflammatory cytokines). Transgenic and knockout strains of mice are used to evaluate specific molecular contributions to the progression of inflammation.
- R.W. Himes and C.W. Smith. 2009. TLR2 is critical for diet-induced metabolic syndrome in a murine model. FASEB J. (on line October 19, 2009)
- S.E. Byeseda, A.R. Burns, S. Dienfferbaugher, R.E. Rumbaut, C.W. Smith, and Z. Li. ICAM-1 is necessary for epithelial recruitment of γδ T cells and efficient corneal wound healing. Am.J.Pathol. 175:571-579, 2009.
- H. Wu, R.M. Gower, H. Wang, X.Y. Perrard, D.C. Bullard, A.R. Burns, C.W. Smith, S.I. Simon C.M. Ballantyne. Functional role of CD11c+ monocytes in atherogenesis associated with hypercholesterolemia. Circulation 119:2708-2717, 2009.
- M.S. Desai, M.M Mariscalco, A. Tawil, J.G. Vallejo and C.W. Smith. 2008. Atherogenic diet-induced hepatitis is partially dependent on murine TLR4. J.Leuk.Biol. 83:1336-1344, 2008.
- Z. Li, A.R. Burns, R.E. Rumbaut, and C.W. Smith. 2007. γδT cells are necessary for platelet and neutrophil accumulation in limbal vessels and efficient epithelial repair following corneal abrasion. Am.J.Pathol. 171:838-845.
- H. Wu, S. Ghosh, X.D. Perrard, G. Thakker, J. F. Sweeney, L. C. B. Chan, C.W. Smith, C. M. Ballantyne. 2007. T-cell accumulation and regulated on activation, normal T cell expressed and secreted upregulation (RANTES) in adipose tissue in obesity. Circulation 115:1029-38.
- A.L. Gonzalez, W. El-Bjeirami, J.L. West, L.V. McIntire, and C.W. Smith. 2007. Transendothelial migration enhances integrin dependent human neutrophil chemokinesis. J.Leuk.Biol. 81:686-95
- D.K. Brake, E.O. Smith, H. Mersmann, C.W. Smith, and R. Robker. 2006. ICAM-1 expression in adipose tissue: Effects of diet-induced obesity in mice. Am.J.Physiol.Cell Physiol. 291:C1232-9.
- Z. Li, R.E. Rumbaut, A.R. Burns, and C.W. Smith. 2006. Platelet response to corneal abrasion is necessary for acute inflammation and efficient re-epithelialization. Invest.,Opthalmol.Vis.Sci. 47:4794-4802.
- Z. Li, A.R. Burns, and C.W. Smith. 2006. LFA-1-dependent inhibition of corneal wound healing. Am.J.Pathol. 169:1590-1600.
For a complete list of Dr. Smith's publications, visit PubMed.
C. Wayne Smith, M.D.
Departments of Pediatrics, Pathology & Immunology, and Medicine
Baylor College of Medicine
Children's Nutrition Research Center, Rm 6014
Houston, Texas 77030, U.S.A.