CCR Expression of Bronchoalveolar Lavage Fluid (BALF) Neutrophils and Chemotactic Activity of BALF

  • Choi, Eu-Gene (Department of Respiratory Internal Medicine, College of Medicine, Konyang University) ;
  • Yang, Eun-Ju (Department of Clinical Laboratory Science, College of Health and Therapy, Daegu Hanny University) ;
  • Kim, Dong-Hee (Department of Pathology, College of Oriental Medicine, Daejeon University) ;
  • Lee, Ji-Sook (Department of Clinical Laboratory Science, Wonkwang Health Science University) ;
  • Kim, In-Sik (Department of Biomedical Laboratory Science, School of Medicine, Eulji University)
  • Received : 2011.02.07
  • Accepted : 2011.03.20
  • Published : 2011.03.31

Abstract

Asthma is an inflammatory airway disease and is characterized by the releases of inflammatory mediators including chemokines. They are mainly associated with the recruitment, activation and dysregulation of specific inflammatory cells, especially neutrophils in neutrophilic asthma. CC chemokines bind to CC chemokine receptors (CCRs) in the surface of their target cells. The aims of this study are to examine the CCR expression in neutrophils of bronchoalveolar lavage fluid (BALF) of asthmatic patients and to determine the alternation of migration and apoptosis of neutrophils by the BALF. We demonstrate that CCR3 strongly expresses in BALF neutrophils of asthmatic patients as compared to other CCRs and increases during apoptosis of the BALF neutrophils. The migration of asthmatic blood neutrophils increases in response to asthmatic BALF as compared to BALF of normal volunteer. In addition, asthmatic BALF includes the higher levels of IL-8 protein than normal BALF and it has no effect on apoptosis of asthmatic blood neutrophils. Taken together, our results indicate that CCR3 expression may be associated with unknown function of asthmatic BALF neutrophils and BALF may be involved in the recruitment of neutrophils into the airway, but not in the neutrophils apoptosis.

Keywords

References

  1. Bonecchi R, Polentarutti N, Luini W, Borsatti A, Bernasconi S, Locati M, Power C, Proudfoot A, Wells TNC, Mackay C. Up-regulation of CCR1 and CCR3 and induction of chemotaxis to CC chemokines by IFN-$\gamma$ in human neutrophils. J Immunol. 1999. 162: 474-479.
  2. Braman SS. The global burden of asthma. Chest 2006. 130: 4S -12S. https://doi.org/10.1378/chest.130.1_suppl.4S
  3. Busse WW, Rosenwasser LJ. Mechanisms of asthma. J Allergy Clin Immunol. 2003. 111: S799-S804. https://doi.org/10.1067/mai.2003.158
  4. Cheng SS, Lai JJ, Lukacs NW, Kunkel SL. Granulocyte macrophage colony stimulating factor up-regulates CCR1 in human neutrophils. J Immunol. 2001. 166: 1178-1184. https://doi.org/10.4049/jimmunol.166.2.1178
  5. Culpitt SV, de Matos C, Russell RE, Donnelly LE, Rogers DF, Barnes PJ. Effect of theophylline on induced sputum inflammatory indices and neutrophilc in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2002. 165: 1371-1376,
  6. Hartl D, Krauss-Etschmann S, Koller B, Hordijk PL, Kuijpers TW, Hoffmann F, Hector A, Eber E, Marcos V, Bittmann I, Eickelberg O, Griese M, Roos D. Infiltrated neutrophils Acquire novel chemokine receptor expression and chemokine responsiveness in chronic inflammatory lung diseases. J Immunol. 2008. 181: 8053-8067. https://doi.org/10.4049/jimmunol.181.11.8053
  7. Holgate ST. Pathogenesis of asthma. Clin Exp Allergy 2008. 38: 872-897. https://doi.org/10.1111/j.1365-2222.2008.02971.x
  8. Holmes WE, Lee J, Kuang WJ, Rice GC, Wood WI. Structure and functional expression of a human interleukin-8 receptor. Science 1991. 253: 1278-1280. https://doi.org/10.1126/science.1840701
  9. Jatakanon A, Uasuf C, Maziak W, Lim S, Chung KF, Barnes PJ. Neutrophilic inflammation in severe persistent asthma. Am J Respir Crit Care Med. 1999. 160: 1532-1539. https://doi.org/10.1164/ajrccm.160.5.9806170
  10. Lee JS, Yang EJ, Ryang YS, Kim IS. Chemotactic effect of leukotactin-1/CCL15 on human neutrophils. J Exp Biomed Sci. 2006. 12: 145-151.
  11. Montecucco F, Steffens S, Burger F, Da Costa A, Bianchi G, Bertolotto M, Mach F, Dallegri F, Ottonello L. Tumor necrosis factor-α (TNF-$\alpha$) induces integrin CD11b/CD18 (Mac-1) up-regulation and migration to the CC chemokine CCL3 (MIP-$1 \alpha$) on human neutrophils through defined signaling pathways. Cell Signal. 2008. 20: 557-568. https://doi.org/10.1016/j.cellsig.2007.11.008
  12. Murdoch C, Finn A. Chemokine receptors and their role in inflammation and infectious diseases. Blood 2000. 95: 3032 -3043.
  13. Ordonez CL, Shaughnessy TE, Matthay MA, Fahy JV. Increased neutrophil numbers and IL-8 levels in airway secretions in acute severe asthma. Am J Respir Crit Care Med. 2000. 161: 1185-1190. https://doi.org/10.1164/ajrccm.161.4.9812061
  14. Palmqvist C, Wardlaw AJ, Pradding P. Chemokines and their receptors as potential targets for the treatment of asthma. Br J Pharmacol. 2007. 151: 725-736. https://doi.org/10.1038/sj.bjp.0707263
  15. Romagnani S. Cytokines and chemoattractants in allergic inflammation. Mol Immunol. 2001. 38: 881-885.
  16. Sampson AP. The role of eosinophils and neutrophils in inflammation. Clin Exp Allergy 2000. 30(Sup 1): 22-27. https://doi.org/10.1046/j.1365-2222.2000.00092.x
  17. Savill JS, Wyllie AH, Henson JE, Walport MJ, Henson PM, Haslett C. Macrophage phagocytosis of aging neutrophils in inflammation. Programmed cell death in the neutrophil leads to its recognition by macrophage. J Clin Invest. 1989. 83:865-875. https://doi.org/10.1172/JCI113970
  18. Scheel-Toellner D, Wang KQ, Webb PR, Wong SH, Craddock R, Assi LK, Salmon M, Lord JM. Early events in spontaneous neutrophil apoptosis. Biochem Soc Trans. 2004. 32: 461-464. https://doi.org/10.1042/BST0320461
  19. Youn BS, Zhang SM, Lee EK, Park DH, Broxmeyer HE, Murphy PM, Locati M, Pease JE, Kim KK, Antol K, Kwon BS. Molecular cloning of leukotactin-1: a novel human betachemokine, a chemoattractant for neutrophils, monocytes, and lymphocytes, and a potent agonist at CC chemokine receptors 1 and 3. J Immunol. 1997. 59: 5201-5205..