Platelet Endothelial Cell Adhesion Molecule-1 Polymorphism in Patients with Bronchial Asthma
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Abstract
Asthma is considered as a chronic inflammatory airway disease and defined as increased tracheobronchial responsiveness to variety of stimuli. Edema and inflammatory cell infiltration in airway is observed in the asthmatic patients. One of the essential changes in inflammation is adhesion of leukocyte to endothelium and transmigration of leukocytes to the sites of inflammation. Unfortunately, little is known about the role of platelet endothelial cell adhesion molecule-1 (PECAM-1) polymorphism in asthma inflammatory process. The purpose of this study was to determine whether PECAM-1 polymorphisms affect the risk of asthma or not.Forty-five asthmatic patients (including 27 men and 18 women) and 45 healthy volunteers (11 men and 34 women) were studied. To determine the severity of the asthmas situation, a questionnaire was prepared asking the following information: age, sex, clinical signs and symptoms and past medical history. All subjects were genotyped for PECAM-1 polymorphism by using amplification refractory mutation system -polymerase chain reaction (ARMS-PCR). The genotype distribution of PECAM-1 80 Val/Met polymorphism in all asthmatic patients were Val/Val while non asthmatic controls were 95.6% Val/Val and 4.4% Val/Met. However, these differences were not statistically significant (p<0.05). The allele and genotype frequencies of PECAM-1 125 Val/Leu polymorphism were significantly different between asthmatic patients and controls. On the other hand, the presence of 125 Leu allele was associated with an increasing risk of asthma with an odds ratio of 2.8 (95% CI; 1.5-5.3, p=0.002). Our findings suggest that the PECAM-1 125 Val/leu polymorphism might be a genetic factor that may be associated with asthma.
1. Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, et al. Harrison‘s principles of internal medicine. 18th ed. New York: McGraw-Hill, 2012:2102-15.
2. Holgate ST. Novel targets of therapy in asthma. Curr Opin Pulm Med 2009; 15(1):63-71.
3. Adcock IM, Caramori G, Chung KF. New targets for drug development in asthma. Lancet 2008;372(9643):1073-87.
4. Holgate ST, Polosa R. Treatment strategies for allergy and asthma. Nat Rev Immunol 2008; 8(3):218-230.
5. Afshar R, Medoff BD, Luster AD. Allergic asthma: a tale of many T cells. Clin Exp Allergy 2008; 38(12):1847-57.
6. Etzioni A, Stiehm ER, Feldweg AM. Leukocyte- endothelial adhesion in the pathogenesis of inflammation. up to date 17.3.
7. Yan HC, Baldwin HS, Sun J, Buck CA, Albelda SM,DeLisser HM. Alternative splicing of a specific cytoplasmic exon alters the binding characteristics of murine platelet/endothelial cell adhesion molecule-1 (PECAM-1). J Biol Chem 1995; 270(40):23672-80.
8. Muller WA, Berman ME, Newman PJ, DeLisser HM, Albelda SM. Aheterophilic adhesion mechanism for platelet/endothelial cell adhesion molecule 1 (CD31). J Exp Med 1992; 175(5):1401-04.
9. Buckley CD, Doyonnas R, Newton JP, Blystone SD, Brown EJ, Watt SM, et al. Identification of alpha v beta 3 as a heterotypic ligand for CD31/PECAM-1. J Cell Sci 1996; 109(Pt 2):437-45.
10. Piali L, Hammel P, Uherek C, Bachmann F, Gisler RH, Dunon D, et al. CD31/PECAM-1 is a ligand for alpha v beta 3 integrin involved in adhesion of leukocytes to endothelium. J Cell Biol 1995; 30(2):451-60.
11. Wong CW, Wiedle G, Ballestrem C, Wehrle-Haller B,Etteldorf S, Bruckner M, et al. PECAM-1/CD31 trans- homophilic binding at the intercellular junctions is independent of its cytoplasmic domain; evidence for heterophilic interaction with integrin alphavbeta3 in Cis. Mol Biol Cell 2000; 11(9):3109-21.
12. Deaglio S, Morra M, Mallone R, Ausiello CM, Prager E, Garbarino G, et al. Human CD38 (ADP-ribosyl cyclase) is a counter-receptor of CD31, an Ig superfamily member. J Immunol 1998; 160(1):395-402.
13. Sachs UJ, Andrei-Selmer CL, Maniar A, Weiss T, Paddock C, Orlova VV, et al. The neutrophil specific antigen CD177 is a counter-receptor for endothelial PECAM-1 (CD31). J Biol Chem 2007; 282(32):23603–12.
14. Firestein GS, Budd RC, Harris ED, Mcinnes IB, Ruddy S, Sergent JS. Kelly's textbook of rheumatology. 8th ed. Philadelphia: W.B. Saunders, 2008.
15. Wakelin MW, Sanz MJ, Dewar A, Albelda SM, Larkin SW, Boughton-Smith N, et al. An anti-platelet- endothelial cell adhesion molecule-1 antibody inhibits leukocyte extravasation from mesenteric microvessels in vivo by blocking the passage through the basement membrane. J Exp Med 1996; 184(1):229-39.
16. Wu Y, Stabach P, Michaud M, Madri JA. Neutrophils lacking platelet endothelial cell adhesion molecule-1 exhibit loss of directionality and motility in CXCR2- mediated chemotaxis. J Immunol 2005; 175(6):3484–91.
17. Goodman RS, Kirton CM, Oostingh GJ, Schön MP, Clark MR, Bradley JA, et al. PECAM-1 polymorphism affects monocyte adhesion to endothelial cells. Transplantation 2008; 85(3):471-7.
18. Snider GL, Woolf CR, Kory RC. Criteria for the assessment of reversibility in airway obstruction: Report of the committee on Emphysema, American College of Chest Physicians. Chest 1974; 65(5):552-3.
19. Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, et al. Standardization of spirometery. Eur Respir J 2005; 26(2):319-38.
20. Scheffer AL. Global strategy for asthma management and prevention. NHLB/WHO Workshop Report. National Institute of Health, Betesda MD, 2002, Publication no.92,3659.
21. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988 Feb; 16(3):1215–8.
22. Borozdenkova S, Smith J, Marshall S, Yacoub M, Rose M. Identification of ICAM-1 polymorphism that is associated with protection from transplant associated vasculopathy after cardiac transplantation. Human Immunology J 2001; 62(3):247-55.
23. Sriramarao P, DiScipio RG, Cobb RR, Cybulsky M,Stachnick G, Castaneda D, et al. VCAM-1 is more effective than MAdCAM-1 in supporting eosinophil rolling under conditions of shear flow. Blood 2000;95(2):592-601.
24. Luster AD. Chemokines: chemotactic cytokines that mediate inflammation. N. Engl. J. Med, 1998;338(7):436-45.
25. Newman PJ, Berndt MC, Gorski J, White GC 2nd, Lyman S, Paddock C, et al. PECAM-1 (CD31) cloning and relation to adhesion molecules of the immunoglobulin gene superfamily. Science 1990;247(4947):1219-22.
26. Behar E, Chao NJ, Hiraki DD, Krishnaswamy S, Brown BW, Zehnder JL, et al. Polymorphisms of adhesion molecule CD31 and its role in acute graft-versus-host disease. N Engl J Med 1996; 334(5):286-91.
27. Newton JP, Buckley CD, Jones EY, Simmons DL.Residues on both faces of the first immunoglobulin fold contribute to homophilic binding sites of PECAM-1/CD31. J Biol Chem 1997; 272(33):20555-63.
28. Sun QH, DeLisser HM, Zukowski MM, Paddock C, Albelda SM, Newman PJ. Individually distinct Ig homology domains in PECAM-1 regulate homophilic binding and modulate receptor affinity. J Biol Chem 1996; 271(19):11090–8.
29. Nadi E, Hajilooi M, Zeraati F, Ansari M, Tavana S, Hashemi SH, et al. E-selectin S128R polymorphism leads to severe asthma. Iran J Allergy Asthma Immunol. 2007 Jun; 6(2):49-57.
30. Amirzargar AA, Movahedi M, Rezaei N, Moradi B, Dorkhosh S, Mahloji M, et al. Polymorphism in IL-4 and iLARA confer susceptibility to asthma. J Investig Allergol Clin Immunol 2009; 19(6):433-8.
31. Li L, Yang L, Tang H. Role of CD44 on airway inflammatory response in rats with asthma. Zhongguo Dang Dai Er Ke Za Zhi 2009; 11(2):142-5.
32. Newton JP, Buckley CD, Jones EY, Simmons DL.Residues on both faces of the first immunoglobulin fold contribute to homophilic binding sites of PECAM-1/CD31. J Biol Chem 1997; 272(33):20555-63.
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| Issue | Vol 11, No 4 (2012) | |
| Section | Articles | |
| Keywords | ||
| Asthma Cell Adhesion Genetic Polymorphism | ||
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