CD44 variant isoforms are specifically expressed on peripheral blood lymphocytes from asthmatic patients

Yang,Chun; Liang,Hongyan; Zhao,Hongli; Jiang,Xiaofeng

doi:10.3892/etm.2012.543

CD44 variant isoforms are specifically expressed on peripheral blood lymphocytes from asthmatic patients

Authors:
- Chun Yang
- Hongyan Liang
- Hongli Zhao
- Xiaofeng Jiang
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Affiliations: Department of Clinical Biochemistry Laboratory, The 4th Affiliated Hospital of Harbin Medical University, Harbin, P.R. China, The Department of Internal Medicine, Harbin Children's Hospital, Harbin, P.R. China
Published online on: April 11, 2012 https://doi.org/10.3892/etm.2012.543
Pages: 79-83

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Abstract

Asthma is a disease characterized by chronic airway inflammation, and Th2 cells play a critical role in initiating and sustaining asthmatic inflammation. It has been shown that CD44 expressed on CD4+ T cells plays a critical role in the accumulation of antigen-specific Th2 cells in the development of airway hyperresponsiveness induced by antigen challenge in the airways. The aim of this study was to determine whether there are specific CD44 variant isoforms (CD44v) expressed on lymphocytes from asthmatic patients. We collected whole blood samples from 103 normal subjects, 165 subjects with asthma and 104 with pneumonia. Peripheral blood lymphocyte isolation was performed, and total RNA was extracted from the isolated lymphocytes, using nested PCR for specific CD44v amplification on lymphocytes. Demographic variables were analyzed using linear regression in order to determine whether the expression of CD44v was correlated with these demographic features. The nested PCR results revealed that CD44v5 was expressed by 55.2% of asthma patients, which was significantly higher than levels of expression in the other groups. Lower percentages of individuals in the normal subject group exhibited expression of CD44v5 and CD44v6. The data demonstrated that the percentage of individuals in the pneumonia group expressing CD44v5 was 29.0%, but a higher percentage of these patients expressed CD44v6. CD44v5 expression was positively correlated with IgE levels (p=0.032) in the asthmatic patient group, and CD44v6 was significantly positively correlated with the neutrophil count (p<0.05). CD44v5 was expressed by a higher proportion of asthmatic patients than other subjects and thus may play an important role in the pathogenesis of asthma. These findings may offer a new target for the diagnosis and treatment of asthma and may also provide insights into the mechanisms of asthma development.

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1	Bochner BS, Undem BJ and Lichtenstein LM: Immunological aspects of allergic asthma. Annu Rev Immunol. 12:2951994. View Article : Google Scholar : PubMed/NCBI
2	Fabbri LM, Romagnoli M, Corbetta L, et al: Differences in airway inflammation in patients with fixed airflow obstruction due to asthma or chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 167:418–424. 2003. View Article : Google Scholar : PubMed/NCBI
3	Robinson DS, Hamid Q, Ying S, Tsicopoulos A, Barkans J, et al: Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma. N Engl J Med. 326:2981992. View Article : Google Scholar : PubMed/NCBI
4	Shalaby KH and Martin JG: Overview of asthma: the place of the T cell. Curr Opin Pharmacol. 10:218–225. 2010. View Article : Google Scholar : PubMed/NCBI
5	DeGrendele HC, Estess P and Siegelman MH: Requirement for CD44 in activated T cell extravasation into an inflammatory site. Science. 278:672–675. 1997. View Article : Google Scholar : PubMed/NCBI
6	Katoh S, Ishii N, Nobumoto A, et al: Galectin-9 inhibits CD44-hyaluronan interaction and suppresses a murine model of allergic asthma. Am J Respir Crit Care Med. 176:27–35. 2007. View Article : Google Scholar : PubMed/NCBI
7	Katoh S, Kaminuma O, Hiroi T, et al: CD44 is critical for airway accumulation of antigen-specific Th2, but not Th1, cells induced by antigen challenge in mice. Eur J Immunol. 41:3198–3207. 2011. View Article : Google Scholar : PubMed/NCBI
8	Goodfellow PN, Banting G, Wiles MV, et al: The gene, MIC4, which controls expression of the antigen defined bymonoclonal antibody F10.44.2 is on human chromosome 11. Eur J Immunol. 12:659–663. 1982. View Article : Google Scholar : PubMed/NCBI
9	Ponta H, Sherman L and Herrlich PA: CD44: from adhesion molecules to signalling regulators. Nat Rev Mol Cell Biol. 4:33–45. 2003. View Article : Google Scholar : PubMed/NCBI
10	Denhardt DT, Noda M, O’Regan AW, et al: Osteopontin as a means to cope with environmental insults: regulation of inflammation, tissue remodeling, and cell survival. J Clin Invest. 107:1055–1061. 2001. View Article : Google Scholar : PubMed/NCBI
11	Bennett KL, Jackson DG, Simon JC, et al: CD44 isoforms containing exon v3 are responsible for the presentation of heparin binding growth factor. J Cell Biol. 128:687–698. 1995. View Article : Google Scholar : PubMed/NCBI
12	Xue J, Xu Y and Zhang Z: Lymphocyte apoptosis in asthmatic patients and its molecular mechanism. Zhonghua Jie He He Hu Xi Za Zhi. 22:555–557. 1999.(In Chinese).
13	Lamb JP, James A, Carroll N, et al: Reduced apoptosis of memory T-cells in the inner airway wall of mild and severe asthma. Eur Respir J. 26:265–270. 2005. View Article : Google Scholar : PubMed/NCBI
14	Lee JL, Wang MJ, Sudhir PR, et al: Osteopontin promotes integrin activation through outside-in and inside-out mechanisms: OPN-CD44V interaction enhances survival in gastrointestinal cancer cells. 67:2089–2097. 2007.
15	Hegde VL, Singh NP, Prakash S, et al: CD44 mobilization in allogeneic dendritic cell-T cell immunological synapse plays a key role in T cell activation. J Leukoc Biol. 84:134–142. 2008. View Article : Google Scholar : PubMed/NCBI
16	Xavier R, Brennan T, Li Q, et al: Membrane compartmentation is required for efficient T cell activation. Immunity. 8:723–732. 1998. View Article : Google Scholar : PubMed/NCBI
17	Viola A, Schroeder S, Sakakibara Y, et al: T lymphocyte costimulation mediated by reorganization of membrane microdomains. Science. 283:680–682. 1999. View Article : Google Scholar : PubMed/NCBI
18	Neame SJ, Uff CR, Sheikh H, et al: CD44 exhibits a cell type dependent interaction with Triton X-100 insoluble, lipid rich, plasma membrane domains. J Cell Sci. 108:3127–3135. 1995.PubMed/NCBI
19	Ilangumaran S, Briol A and Hoessli DC: CD44 selectively associates with active Src family protein tyrosine kinases Lck and Fyn in glycosphingolipid-rich plasma membrane domains of human peripheral blood lymphocytes. Blood. 91:3901–3908. 1998.
20	Foger N, Marhaba R and Zoller M: Involvement of CD44 in cytoskeleton rearrangement and raft reorganization in T cells. J Cell Sci. 114:1169–1178. 2001.PubMed/NCBI
21	Mojtabavi N, Dekan G, Stingl G and Epstein MM: Long-lived Th2 memory in experimental allergic asthma. J Immunol. 169:4788–4796. 2002. View Article : Google Scholar : PubMed/NCBI
22	Günthert U and Johansson B: CD44 – a protein family involved in autoimmune diseases and apoptosis. Immunologist. 8:106–109. 2001.
23	Mielgo A, van Driel M, Bloem A, et al: A novel antiapoptotic mechanism based on interference of Fas signaling by CD44 variant isoforms. Cell Death Differ. 13:465–477. 2006. View Article : Google Scholar : PubMed/NCBI
24	Wittig BM, Johansson B, Zoller M, et al: Abrogation of experimental colitis correlates with increased apoptosis in mice deficient for CD44v7. J Exp Med. 191:2053–2063. 2000. View Article : Google Scholar : PubMed/NCBI
25	Hoffmann U, Heilmann K, Hayford C, et al: CD44v7 ligation downregulates the inflammatory immune response in Crohn’s disease patients by apoptosis induction in mononuclear cells from the lamina propria. Cell Death Differ. 14:1542–1551. 2007.PubMed/NCBI