Evaluation of Fc Receptor Gene Variants in Bovine Neutrophils
Abstract
The objectives of this study were to detect FcR I, FcR II and their sub isoforms in cows, evaluate genetic variation, the impact of IgG binding on transcription of FcγR and secreted levels of phosphorylated Syk. Neutrophils contain a heterogeneous population of Fc receptors (FcR). The FcγRs (I, II and sub isoforms) bind specifically to IgG molecules and stimulate effector cells to destroy pathogens by phagocytosis and intracellular killing. The SYK kinase is critical for FcγR-mediated phagocytosis and signal transduction. Blood was collected from Holstein-Friesian (n=6) and JerseyXHolstein (n=4) lactating cows at the North Carolina A&T State University dairy farm. The somatic cell count and packed cell volume were used to evaluate overall health. DNA was isolated from blood stored on FTA cards. Specific primers for FcRI (CD64), FcRII (CD32) and FcRII sub-isoforms were used to amplify Fc receptor genes. The housekeeping gene GAPDH was used to normalize the data. Amplified products were separated on a 1% agarose gel and observed following staining with ethidium bromide. Polymorphisms were evaluated by SSCP analysis. Neutrophils treated with whole bovine IgG molecules were used for q-PCR. FcRI and FcRIIc were detected in all cows. Packed cell volume remained within the range of a healthy cow. All genes were transcribed. An increase was observed in the transcription of FcγRII in Jersey X Holstein cows, and a significant increase was observed in the Syk protein expression of Jersey X Holstein cows (p<0.05) when compared to Holstein-Friesian cows. Heterogeneity in FcγR gene expression may be related to breed differences in cows and impact downstream cellular function following binding of IgG to Fc receptors. The activating (FcRIIa) and inhibitory (FcRIIb) respectively were detected only in Holstein × Jersey crossbred cows regardless of SCC. Further studies are needed to evaluate the effect of FcR gene polymorphism on the cellular response in cattle. These results have implications for control of inflammatory diseases such as mastitis in cattle.
Keywords
Full Text:
PDFReferences
Abatepaulo, A. R., Caetano, A. R., Mendes Jr, C. T., Carvalho, W. A., Ferreira, B. R., & De Miranda Santos, I. F. (2008). Detection of SNPs in bovine immune-response genes that may mediate resistance to the cattle tick Rhipicephalus (Boophilus) microplus. Animal Genetics, 39(3), 328-329.
Aderem, A., & Underhill, D. M. (1999). Mechanisms Of Phagocytosis In Macrophages. Annual Review of Immunology, 17(1), 593-623.
Aiello, S., & Mays, A. (1998). The Merck veterinary manual (8th ed., pp. 2190-2191).
Whitehouse Station, NJ: Merck &, in cooperation with Merial. Barrow, A., & Trowsdale, J. (2006). Correction: You say ITAM and I say ITIM, let's call the whole thing off: The ambiguity of immune receptor signaling. European Journal of Immunology, 36(8), 2276-2276.
Beale, D., & Feinstein, A. (1976). Structure and function of the constant regions of immunoglobulins. Quarterly Reviews of Biophysics, 9(02), 135.
Berkowicz, E. W., Magee, D. A., Berry, D. P., Sikora, K. M., Howard, D. J., Mullen, M. P., ... MacHugh, D. E. (2011). Single nucleotide polymorphisms in the imprinted bovine insulin-like growth factor 2 receptor gene (IGF2E) are associated with body size traits in irish holstein-friesian cattle. Animal Genetics: Immunogenetics, Molecular Genetics and Fundamental Genomics, 1-7.
Bewarder, N., Weinrich, V., Budde, P., Hartmann, D., Flaswinkel, H., Reth, M., & Frey, J. (1996). In vivo and in vitro specificity of protein tyrosine kinases for immunoglobulin G receptor phosphorylation. Molecular and Cellular Biology, 16(9), 4735-4743.
Bournazos, S., Woof, J. M., Hart, S. P., & Dransfield, I. (2009). Functional and clinical consequences of Fc receptor polymorphic and copy number variants. Clinical & Experimental Immunology, 157(2), 244-254.
Bradley, A. (2002). Bovine Mastitis: An Evolving Disease. The Veterinary Journal, 164(2), 116-128.
Bradshaw, J. M. (2010). The Src, Syk, and Tec family kinases: Distinct types of molecular switches. Cellular Signalling, 22(8), 1175-1184.
Carlson, G. P., & Kaneko, J. J. (1973). Isolation of leukocytes from bovine peripheral blood. Experimental Biology and Medicine, 142(3), 853-856.
Cohen, I. R., & Norins, L. C. (1968). Antibodies of the IgG, IgM, and IgA classes in newborn and adult sera reactive with gram-negative bacteria. Journal of Clinical Investigation, 47(5), 1053-1062.
Cooney, D. S., Phee, H., Jacob, A., & Coggeshall, K. (2001). Signal Transduction by Human-Restricted FcγRIIa Involves Three Distinct Cytoplasmic Kinase Families Leading to Phagocytosis. The Journal of Immunology, 167(2), 844-854.
Edberg, J. C., Moon, J. J., Chang, D. J., & Kimberly, R. P. (1998). Differential regulation of human neutrophil Fc gamma receptor IIa (CD 32) and Fc gamma receptor IIIb (CD 16)-induced Ca Transients. The Journal of Biological Chemistry, 273(14), 8071-8079.
Firth, M. A., Chattha, K. S., Hodgins, D. C., & Shewen, P. E. (2010). Multiple bovine FcγRIIb sub-isoforms generated by alternative splicing. Veterinary Immunology and Immunopathology, 135(1-2), 43-51.
Flesch, B., Bauer, F., & Neppert, J. (1998). Rapid typing of the human Fc gamma receptor IIA polymorphism by polymerase chain reaction amplification with allele-specific primers. Tranfusion, 38(2), 174-176.
Fox, L. (2009). Prevalence, incidence and risk factors of heifer mastitis. Veterinary Microbiology, 134(1-2), 82-88.
Fridman, W. H. (1991). Fc receptors and Immunoglobulin binding factors. The Federation of American Societies for Experimental Biology (FASEB), 5, 2684-2690.
Ganesan, L. P. (2003). The protein-tyrosine phosphatase SHP-1 associates with the
phosphorylated immunoreceptor tyrosine-based activation motif of FcγRIIa to modulate signaling events in myeloid cells. The Journal of Biological Chemistry, 278(37), 35710-5717.
Gerber, J. S., & Mosser, D. M. (2001). Stimulatory and inhibitory signals originating from the macrophage Fc gamma receptors. Microbes and Infection, 3, 131-139.
Ghazizadeh, S. J., Bolen, B., & Fleit, H. B. (1994). Physical and functional association of Src-related protein tyrosine kinases with Fc gamma RII in monocytic THP-1 cells. The Journal of Biological Chemistry, 269, 8878-8884.
Halushka, M. K., Fan, J., Bentley, K., Hsie, L., Shen, N., Weder, A., Chakravarti, A. (1999). Nature America Inc., 22, 239-247.
Huang, Z., Hunter, S., Kim, M., Indik, Z. K., & Schreiber, A. D. (2003). The effect of phosphatases SHP-1 and SHIP-1 on signaling by the ITIM- and ITAM-containing Fcγ receptors FcγRIIB and FcγRIIA. Journal of Leukocyte Biology, 73(6), 823-829.
Ibarrola, I., Vossebeld, P., Homberg, C., Thelen, M., Ross, D., & Verhoeven, A. (1997). Influence of tyrosine phosphorylation on protein interaction with FcγRIIa. Biochimica Et Biophysica Acta (BBA) - Molecular Cell Research, 1357(3), 348-358.
Isakov, N. (1997). ITIMs and ITAMs. Immunologic Research, 16(1), 85-100.
Jiang, Y., Hirose, S., Abe, M., Sanokawa-Akakura, R., Ohtsuji, M., Mi, X., Shirai, T. (2000). Polymorphisms in IgG Fc receptor IIB regulatory regions associated with autoimmune susceptibility. Immunogenetics, 51(6), 429-435.
Kacskovics, I. (2004). Fc receptors in livestock species. Veterinary Immunology and Immunopathology, 102(4), 351-362.
Klungland, H., Gomez-Raya, L., Howard, C. J., Collins, R. A., Rogne, S., & Lien, S. (1997). Mapping of bovine FcγR (FCGR) genes by sperm typing allows extended use of human map information. Mammalian Genome, 8(8), 573-577.
Konstantinos, K. V., Panagiotis, P., Antonios, V. T., Agelos, P., & Argiris, N. V. (2008). PCR–SSCP: A Method for the Molecular Analysis of Genetic Diseases. Molecular Biotechnology, 38(2), 155-163.
Liu, Y., Qiao, S., Wang, A., Chang, J., Chen, Y., Yang, S., Zhang, G. (2011). Cloning and characterization of ovine immunolglobulin G Fc receptor III. Veterinary Immunology and Immunopathology, 139, 282-288.
Lucy, M. (2001). Reproductive Loss in High-Producing Dairy Cattle: Where Will It End? Journal of Dairy Science, 84(6), 1277-1293.
Ma, Y., Ke, C., Wan, Z., Li, Z., Cheng, X., Wang, X., ... & Zhao, Y. (2018). Truncation of the Murine Neonatal Fc Receptor Cytoplasmic Tail Does Not Alter IgG Metabolism or Transport In Vivo. The Journal of Immunology, ji1700924.
Majeed, M., Caveggion, E., Lowell, C., & Berton, G. (2001). Role of Src kinases and Syk in Fcγ receptor-mediated phagocytosis and phagosome-lysosome fusion. Journal of Leukocyte Biology, 70(5), 801-811.
McGaha, T. L., Karlsson, M. C., & Ravetch, J. V. (2008). FcγRIIB Deficiency Leads to Autoimmunity and a Defective Response to Apoptosis in Mrl-MpJ Mice. The Journal of Immunology, 180(8), 5670-5679.
Mellor, J.D., Brown, M.P., Irving, H.R., Zalcberg,J.R., & Dobrovic, A.(2013). A critical review of the role of Fc gamma receptor polymorphism in the response to monoclonal antibodies in cancer. Journal of Hematology & Oncology, 6 (1), 1-10. https://doi.org/10.1186/1756-8722-6-1
Mina-osorio, P., & Ortega, E. (2004). Signal regulators in FcR-mediated activation of leukocytes? Trends in Immunology, 25(10), 529-535.
Mishima, T., Kurasawa, G., Ishikawa, G., Mori, M., Kawahigashi, Y., Ishikawa, T., ... Takizawa, T. (2007). Endothelial Expression of Fc Gamma Receptor IIb in the Full-term Human Placenta. Placenta, 28(2-3), 170-174.
Morton, H. (2005). IgA Fc receptors in cattle and horses. Veterinary Immunology and Immunopathology, 108(1-2), 139-143.
Morton, H. C., Pleass, R. J., Storset, A. K., Dissen, E., Williams, J. L., Brandtzaeg, P., & Woof, J. M. (2004). Cloning and characterization of an immunoglobulin A Fc receptor from cattle. Immunology, 111(2), 204-211.
Niemialtowski, M., Nonnecke, B., & Targowski, S. (1988). Phagocytic Activity of Milk Leukocytes During Chronic Staphylococcal Mastitis. Journal of Dairy Science, 71(3), 780-787.
Nimmerjahn, F., & Ravetch, J. V. (2008). Fcgamma receptors as regulators of immune responses. Nature Reviews. Immunology, 8(1), 34-47.
Paape, M., Bannerman, D., Zhao, X., & Lee, J. (2003). The bovine neutrophil: Structure and function in blood and milk. Veterinary Research, 34(5), 597-627.
Paape,, M., Shafer-Weaver, K., Capuco, A., Oostveldt, K., & Burvenich, C. (2002). Immune Surveillance of Mammary Tissue by Phagocytic Cells. Advances in Experimental Medicine and Biology, 480, 259-277.
Paixao, T., Ferreira, C., Borges, A., Oliveira, D., Lage, A., & Santos, R. (2006). Frequency of bovine (Slc11a1) alleles in Holstein and Zebu breeds. Veterinary Immunology and Immunopathology, 109(1-2), 37-42.
Pan, L., & Pei, P. (2003). Signaling transduction by IgG receptors. Chinese Medical Journal, 116(4), 487-494.
Parsons, S. J., & Parsons, J. T. (2004). Src family kinases, key regulators of signal transduction. Oncogene, 23(48), 7906-7909.
Radha, V., Nambirajan, S., & Swarup, G. (1996). Association of Lyn Tyrosine Kinase with the Nuclear Matrix and Cell-Cycle-Dependent Changes in Matrix-Associated Tyrosine Kinase Activity. European Journal of Biochemistry, 236(2), 352-359.
Raghavan, M., & Bjorkman, P. J. (1996). Fc RECEPTORS AND THEIR INTERACTIONS WITH IMMUNOGLOBULINS. Annual Review of Cell and Developmental Biology, 12(1), 181-220.
Ravetch, J. V., & Bolland, S. (2001). Igg Fc Receptors. Annual Review of Immunology, 19(1), 275-290.
Rodríguez, F., Cai, D., Teng, Y., & Spooner, D. (2011). ASYMMETRIC SINGLE-STRAND CONFORMATION POLYMORPHISM:. American Journal of Botany, 98(7), 1061-1067.
Rupp, R., & Boichard, D. (2000). Relationship of early first lactation somatic cell count with risk of subsequent first clinical mastitis. Livestock Production Science, 62(2), 169-180.
Schroeder, H. W., Jr., & Cavacini, L. (2010). Structure and function of immunoglobulins. Journal of Allergy and Clinical Immunology, 125(2), S348-S348.
Selvaraj, P., Fifadara, N., Nagarajan, S., Cimino, A., & Wang, G. (2004). Functional Regulation of Human Neutrophil Fc γ Receptors. Immunologic Research, 29(1-3), 219-230.
Smith, K. C., & Clatworthy, M. R. (2010). FcγRIIB in autoimmunity and infection: Evolutionary and therapeutic implications. Nature Reviews Immunology, 10(5), 328-343.
Stefanescu, R. N., Olferiev, M., Liu, Y., & Pricop, L. (2004). Inhibitory Fc Gamma Receptors: From Gene to Disease. Journal of Clinical Immunology, 24(4), 315-326.
Swanson, J. A. (2004). The coordination of signaling during Fc receptor-mediated phagocytosis. Journal of Leukocyte Biology, 76(6), 1093-1103.
Syvänen, A. (2001). ACCESSING GENETIC VARIATION: GENOTYPING SINGLE NUCLEOTIDE POLYMORPHISMS. NATURE REVIEWS:GENETICS, 2, 930-942.
Takai, T. (2005). Fc Receptors and Their Role in Immune Regulation and Autoimmunity. Journal of Clinical Immunology, 25(1), 1-18.
Thomas, S. M., & Brugge, J. S. (1997). Cellular Functions Regulated By Src Family Kinases. Annual Review of Cell and Developmental Biology, 13(1), 513-609.
Underhill, D. M., & Ozinsky, A. (2002). PHAGOCYTOSIS OF MICROBES: Complexity in Action. Annual Review of Immunology, 20(1), 825-852.
Vignal, A., Milan, D., SanCristobal, M., & Eggen, A. (2002). A review on SNP and other types of molecular markers and their use in animal genetics. Genetics Selection Evolution, 34(3), 275-305.
Vivier, E., & Daeron, M. (1997). Immunoreceptor tyrosine-based inhibition motifs. Immunology Today, 18(6), 286-291.
Wellenberg, G., Van der Poel, W., & Van Oirschot, J. (2002). Viral infections and bovine mastitis: A review. Veterinary Microbiology, 88(1), 27-45.
Worku, M., Paape, M., Filep, R., & Miller, R. (1994). Effect of in vitro and in vivo migration of bovine neutrophils on binding and expression of Fc receptors for IgG2 and IgM. American Journal of Veterinary Medicine, 55(2), 221-226.
Yamamoto, H., Teramoto, H., Uetani, K., Igawa, K., & Shimizu, E. (2001). Stretch induces a growth factor in alveolar cells via protein kinase. Respiration Physiology, 127(2-3), 105-111.
Yan, Y., Li, X., Wang, A., & Zhang, G. (2000). Molecular cloning and identification of full-length cDNA encoding high affinity Fc receptor for bovine IgG. Veterinary Immunology and Immunopathology, 75, 151-159.
Yuan, Z., Li, J., Zhang, L., Zhang, L., Chen, C., Chen, X., Xu, S. (2011). Novel SNPs polymorphism of bovine CACNA2D1 gene and their association with somatic cell score. African Journal of Biotechnology, 10(10), 1789-1793.
Zhao, X., & Lacasse, P. (2008). Mammary tissue damage during bovine mastitis: Causes and control. Journal of Animal Science, 86(13), 57-65.
Geahlen, R. L. 2009. Syk and pTyr’d: Signaling through the B cell antigen receptor. Biochim. Biophys. Acta. 1793: 1115– 1127
Zhang, X., Majlessi, L., Deriaud, E., Leclerc, C., & Lo-Man, R. (2009). Coactivation of Syk kinase and MyD88 adaptor protein pathways by bacteria promotes regulatory properties of neutrophils. Immunity, 31(5), 761-771.
Zhang, D., Qin, J., Li, L., Su, G., Huang, G., Cao, Q., ... & Yang, P. (2018). Analysis of the association between Fc receptor family gene polymorphisms and ocular Behçet’s disease in Han Chinese. Scientific reports, 8(1), 4850.
Refbacks
- There are currently no refbacks.
Copyright (c) 2018 Mulumebet Worku
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
This site is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.