Abstract

Mononuclear leukocyte adherence to endothelium is a pivotal event in the inflammatory phase of arterial diseases such as atherosclerosis. The current model of leukocyte emigration predicts that leukocytes first adhere transiently via selectin receptors with subsequent firm adherence mediated by integrin receptors, triggered to a high avidity state by local stimuli. This proposal will examine the regulation of leukocyte adhesion, focusing on the role of selectin receptors in monocyte emigration in the arterial circulation and the regulation of beta1 integrin affinity. The following Specific Aims are proposed: 1) to determine the role of selectins in mononuclear phagocyte emigration into the arterial wall of rabbits following stimulation with chemotactic agents; 2) to determine the effect of affinity modulation by the activating beta1 MAb 8A2 in vivo; 3) to determine the adhesion pathway involved in beta1 MAb 4B5-stimulated leukocyte adherence to endothelium; 4) to examine mechanisms of high affinity mononuclear leukocyte adhesion; and 5) to determine the cytoskeletal associations of high affinity beta1 receptors.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL018645-22
Application #
5213226
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
22
Fiscal Year
1996
Total Cost
Indirect Cost

  Publications

Wight, Thomas N (2018) A role for proteoglycans in vascular disease. Matrix Biol 71-72:396-420
Kocarnik, Beverly M; Boyko, Edward J; Matsumoto, Alvin M et al. (2016) Baseline estradiol concentration in community-dwelling Japanese American men is not associated with intra-abdominal fat accumulation over 10 years. Obes Res Clin Pract 10:624-632
Nishizawa, Tomohiro; Kanter, Jenny E; Kramer, Farah et al. (2014) Testing the role of myeloid cell glucose flux in inflammation and atherosclerosis. Cell Rep 7:356-365
Wight, Thomas N; Kinsella, Michael G; Evanko, Stephen P et al. (2014) Versican and the regulation of cell phenotype in disease. Biochim Biophys Acta 1840:2441-51
Kang, Inkyung; Yoon, Dong Won; Braun, Kathleen R et al. (2014) Expression of versican V3 by arterial smooth muscle cells alters tumor growth factor ? (TGF?)-, epidermal growth factor (EGF)-, and nuclear factor ?B (NF?B)-dependent signaling pathways, creating a microenvironment that resists monocyte adhesion. J Biol Chem 289:15393-404
Ruppert, S M; Hawn, T R; Arrigoni, A et al. (2014) Tissue integrity signals communicated by high-molecular weight hyaluronan and the resolution of inflammation. Immunol Res 58:186-92
Wight, Thomas N; Kang, Inkyung; Merrilees, Mervyn J (2014) Versican and the control of inflammation. Matrix Biol 35:152-61
Reed, May J; Damodarasamy, Mamatha; Chan, Christina K et al. (2013) Cleavage of hyaluronan is impaired in aged dermal wounds. Matrix Biol 32:45-51
Yan, Fang; Liu, Liping; Dempsey, Peter J et al. (2013) A Lactobacillus rhamnosus GG-derived soluble protein, p40, stimulates ligand release from intestinal epithelial cells to transactivate epidermal growth factor receptor. J Biol Chem 288:30742-51
Rutnam, Zina Jeyapalan; Wight, Thomas N; Yang, Burton B (2013) miRNAs regulate expression and function of extracellular matrix molecules. Matrix Biol 32:74-85

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