Effects of undenatured whey protein supplementation on CXCL12- and CCL21-mediated B and T cell chemotaxis in diabetic mice

Lipids in Health and Disease

Ali Metwalli³  Mohamed Mohany¹  Gamal Badr² 

[1] Zoology Department, College of Science, King Saud University, Saudi Arabia;Zoology Department, Faculty of Science, Assiut University, Egypt;Food Science Department, College of Agriculture and Food Science, King Saud University, Saudi Arabia

关键词: whey protein;    T cells;    F-actin polymerization;    diabetes mellitus;    chemotaxis;    B cells;   

Others  :  1212445
DOI  :  10.1186/1476-511X-10-203

 received in 2011-10-11, accepted in 2011-11-09,  发布年份 2011

【 摘 要 】

Background

Long and persistent uncontrolled diabetes tends to degenerate the immune system and leads to an increased incidence of infection. Whey proteins (WPs) enhance immunity during early life and have a protective role in some immune disorders. In this study, the effects of camel WP on the chemotaxis of B and T cells to CXCL12 and CCL21 in diabetic mice were investigated.

Results

Flow cytometric analysis of the surface expressions of CXCR4 (CXCL12 receptor) and CCR7 (CCL21 receptor) on B and T cells revealed that the surface expressions of CXCR4 and CCR7 were not significantly altered in diabetic and WP-supplemented diabetic mice compared with control mice. Nevertheless, B and T lymphocytes from diabetic mice were found to be in a stunned state, with a marked and significant (P < 0.05) decrease in CXCL12- and CCL21-mediated actin polymerization and subsequently, a marked decrease in their chemotaxis. WP supplementation in the diabetes model was found to significantly increase CXCL12- and CCL21-mediated actin polymerization and chemotaxis in both B and T cells.

Conclusion

Our data revealed the benefits of WP supplementation in enhancing cytoskeletal rearrangement and chemotaxis in B and T cells, and subsequently improving the immune response in diabetic mice.

【 授权许可】

   
2011 Badr et al; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Thompson CS: Animal models of diabetes mellitus: relevance to vascular complications. Curr Pharm Des 2008, 14:309-324.
• [2]Smitherman KO, Peacock JE: Infectious emergencies in patients with diabetes mellitus. Med Clin North Am 1995, 79:53-77.
• [3]Mikulkova Z, Praksova P, Stourac P, Bednarik J, Strajtova L, Pacasova R, Belobradkova J, Dite P, Michalek J: Numerical defects in CD8+CD28- T-suppressor lymphocyte population in patients with type 1 diabetes mellitus and multiple sclerosis. Cell Immunol 2010, 262:75-9.
• [4]Zeidler A, Shargill NS, Chan TM: Peripheral insulin insensitivity in the hyperglycemic athymic nude mouse: similarity to noninsulin-dependent diabetes mellitus. Proc Soc Exp Biol Med 1991, 196:457-460.
• [5]Toldi G, Vásárhelyi B, Kaposi A, Mészáros G, Pánczél P, Hosszufalusi N, Tulassay T, Treszl A: Lymphocyte activation in type 1 diabetes mellitus: the increased significance of Kv1.3 potassium channels. Immunol Lett 2010, 133:35-41.
• [6]Bradshaw EM, Raddassi K, Elyaman W, Orban T, Gottlieb PA, Kent SC, Hafler DA: Monocytes from patients with type 1 diabetes spontaneously secrete proinflammatory cytokines inducing Th17 cells. J Immunol 2009, 183:4432-9.
• [7]Von Andrian U, Mackay C: T-cell function and migration: two sides of the same coin. N Engl J Med 2000, 343:1020-1034.
• [8]Gunn MD, Kyuwa S, Tam C, Kakiuchi T, Matsuzawa A, Williams LT, Nakano H: Mice lacking expression of secondary lymphoid organ chemokine have defects in lymphocyte homing and dendritic cell localization. J Exp Med 1999, 189:451-460.
• [9]Badr G, Borhis G, Treton D, Richard Y: IFN-alpha enhances human B-cell chemotaxis by modulating ligand-induced chemokine receptor signaling and internalization. Int Immunol 2005, 17:459-67.
• [10]Pollard TD, Borisy GG: Cellular motility driven by assembly and disassembly of actin filaments. Cell 2003, 112:453-65.
• [11]Balbis E, Patriarca S, Furfaro A, Millanta S, Sukkar GS, Marinari MU, Pronzato AM, Cottalasso D, Traverso N: Whey proteins influence hepatic glutathione after CCl4 intoxication. Toxico Ind Heal 2009, 25:325-328.
• [12]Gauthier SF, Pouliot Y, Saint-Sauveur D: Imunomodulatory peptides obtained by the enzymatic hydrolysis of whey proteins. Inter Dairy J 2006, 16:1315-1323.
• [13]Micke P, Beeh KM, Schlaak JF, Buhl R: Oral supplementation with whey proteins increases plasma glutathione levels of HIV-infected patients. Eur J Clin Invest 2001, 31:171-8.
• [14]Krissansen GW: Emerging health properties of whey proteins and their clinical implications. J Am Coll Nutr 2007, 26:S713-23.
• [15]Beaulieu J, Dupont C, Lemieux P: Whey proteins and peptides: beneficial effects on immune health. Therapy 2006, 3:1-10.
• [16]Rusu D, Drouin R, Pouliot Y, Gauthier S, Poubelle PE: A bovine whey protein extract stimulates human neutrophils to generate bioactive IL-1Ra through a NF-kappaB- and MAPK-dependent mechanism. J Nutr 2010, 140(2):382-91.
• [17]Loss G, Apprich S, Waser M, Kneifel W, Genuneit J, Büchele G, Weber J, Sozanska B, Danielewicz H, Horak E, van Neerven RJ, Heederik D, Lorenzen PC, von Mutius E, Braun-Fahrländer C: GABRIELA study group. The protective effect of farm milk consumption on childhood asthma and atopy: The GABRIELA study. J Allergy Clin Immunol 2011, 128:766-773.
• [18]Castro GA, Maria DA, Bouhallab S, Sgarbieri VC: In vitro impact of a whey protein isolate (WPI) and collagen hydrolysates (CHs) on B16F10 melanoma cells proliferation. J Dermatol Sci 2009, 56:51-7.
• [19]Hamad EM, Taha SH, Abou Dawood AG, Sitohy MZ, Abdel-Hamid M: Protective effect of whey proteins against nonalcoholic fatty liver in rats. Lipids Health Dis 2011, 10:57. BioMed Central Full Text
• [20]Pal S, Ellis V, Ho S: Acute effects of whey protein isolate on cardiovascular risk factors in overweight, post-menopausal women. Atherosclerosis 2010, 212:339-44.
• [21]Sprong RC, Schonewille AJ, van der Meer R: Dietary cheese whey protein protects rats against mild dextran sulfate sodium-induced colitis: role of mucin and microbiota. J Dairy Sci 2010, 93:1364-71.
• [22]Uetrecht AC, Bear JE: Coronins: the return of the crown. Trends Cell Biol 2006, 16:421-426.
• [23]Advani A, Marshall SM, Thomas TH: Increasing neutrophil F-actin corrects CD11b exposure in Type 2 diabetes. Eur J Clin Invest 2004, 34:358-64.
• [24]Gomez TS, Hamann MJ, McCarney S, Savoy DN, Lubking CM, Heldebrant MP, Labno CM, McKean DJ, McNiven MA, Burkhardt JK, Billadeau DD: Dynamin 2 regulates T cell activation by controlling actin polymerization at the immunological synapse. Nat Immunol 2005, 6:261-270.
• [25]Badr G, Sayed D, Alhazza IM, Elsayh KI, Ahmed EA, Alwasel SH: T lymphocytes from malnourished infants are short-lived and dysfunctional cells. Immunobiology 2011, 216:309-15.
• [26]Segal MS, Shah R, Afzal A, Perrault CM, Chang K, Schuler A, Beem E, Shaw LC, Li Calzi S, Harrison JK, Tran-Son-Tay R, Grant MB: Nitric oxide cytoskeletal-induced alterations reverse the endothelial progenitor cell migratory defect associated with diabetes. Diabetes 2006, 55:102-9.
• [27]Aboumrad E, Madec AM, Thivolet C: The CXCR4/CXCL12 (SDF-1) signalling pathway protects non-obese diabetic mouse from autoimmune diabetes. Clin Exp Immunol 2007, 148:432-9.
• [28]Blades MC, Manzo A, Ingegnoli F, Taylor PR, Panayi GS, Irjala H, Jalkanen S, Haskard DO, Perretti M, Pitzalis C: Stromal cell-derived factor 1 (CXCL12) induces human cell migration into human lymph nodes transplanted into SCID mice. J Immunol 2002, 168:4308.
• [29]Lastovicka J, Budinsky V, Spisek R, Bartunková J: Assessment of lymphocyte proliferation: CFSE kills dividing cells and modulates expression of activation markers. Cell Immunol 2009, 256:79-85.
• [30]Rusu D, Drouin R, Pouliot Y, Gauthier S, Poubelle PE: A bovine whey protein extract can enhance innate immunity by priming normal human blood neutrophils. J Nutr 2009, 139:386-93.
• [31]Zhao J, Weiler HA: Long-term effects of gestational diabetes on offspring health are more pronounced in skeletal growth than body composition and glucose tolerance. Br J Nutr 2010, 9:1-9.
• [32]Moratz C, Hayman JR, Gu H, Kehrl JH: Abnormal B-cell responses to chemokines, disturbed plasma cell localization, and distorted immune tissue architecture in Rgs1-/- mice. Mol Cell Biol 2004, 24:5767-75.