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Immunogenetics

, Volume 65, Issue 12, pp 861–871 | Cite as

Nonbactericidal secreted phospholipase A2s are potential anti-inflammatory factors in the mammary gland

  • Eyal SeroussiEmail author
  • Shelly Klompus
  • Maayan Silanikove
  • Oleg Krifucks
  • Fira Shapiro
  • Arieh Gertler
  • Gabriel Leitner
Original Paper

Abstract

The recent burst of duplication and divergence of the bovine PLA2G2D genes is considered typical of immune response genes, and it was recently shown that PLA2G2D is abundantly expressed in mouse leukocytes and acts as an immunosuppressive phospholipase. Analysis of 1,143 Holstein bulls indicated that the four common haplotypes spanning PLA2G2D display copy number variation ranging from 1 to 4 per haploid genome. Association of the fourth haplotype with negative total merit remained significant (P < 0.002) when corrected for population relatedness. We compared the lipase and bactericidal activities of bovine pancreatic PLA2G1B with human PLA2G2A and G2D and bovine PLA2G2D1 and G2D4 proteins, which had been subcloned, expressed, and refolded by us, and the impact of point mutations in the calcium binding site was investigated. All tested phospholipases were ineffective bactericides of Escherichia coli isolated from bovine mastitis. However, in lactating mice treated with E. coli or lipopolysaccharide (LPS), intramammary injection of bovine PLA2G1B relieved visual and histological inflammation and reduced blood levels of infiltrating lactose. Further studies are warranted to determine whether the observed anti-inflammatory effect involves competitive binding of the receptor Pla2r1 which may mimic the LPS resistance effect in Pla2r1-deficient mice.

Keywords

sPLA2s SNP BeadChip Noncatalytic phospholipase like EMMAX CNV Chromatogram peak ratio 

Notes

Acknowledgments

Contribution from the Agricultural Research Organization, Institute of Animal Science, Beit Dagan, Israel, no. 616/12, is acknowledged. This research was supported by a grant from the Research Fund of Israel Dairy Board. We acknowledge the contributions of M. Ron, G. Glick, A. Shirak, J.I. Weller, E. Ezra, and Y. Zeron in providing the data from the BeadChip experiment. Genotyping was performed by A. Schein and N. Avidan, Pharmacogenetics and Translation Medicine Center, the Rappaport Institute for Research in the Medical Sciences, Technion, Haifa, Israel. We thank E. Yakobson for helpful discussion. Histological work was performed by N. Edry, Department of Pathology, Kimron Veterinary Institute, Israel.

Supplementary material

251_2013_738_MOESM1_ESM.pdf (12.1 mb)
ESM 1 (PDF 12384 kb)
251_2013_738_MOESM2_ESM.pdf (463 kb)
ESM 2 (PDF 462 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Eyal Seroussi
    • 1
    Email author
  • Shelly Klompus
    • 1
    • 2
  • Maayan Silanikove
    • 1
    • 2
  • Oleg Krifucks
    • 3
  • Fira Shapiro
    • 1
  • Arieh Gertler
    • 2
  • Gabriel Leitner
    • 3
  1. 1.Institute of Animal Science, AROThe Volcani CenterBeit DaganIsrael
  2. 2.The Robert H. Smith Faculty of Agriculture, Food and EnvironmentThe Hebrew University of JerusalemJerusalemIsrael
  3. 3.National Mastitis Reference CenterKimron Veterinary InstituteBeit DaganIsrael

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