BOVINE GRANULOCYTE CHEMOTACTIC PROTEIN-2 IS SECRETED BY THE ENDOMETRIUM IN RESPONSE TO INTERFERON-TAU (IFN-TAU)

Interferon-tau (IFN-tau) is secreted by the bovine conceptus and may r egulate synthesis of uterine endometrial cytokines to provide an envir onment that is conducive to embryo development and implantation. Inter feron-tau stimulates secretion of an 8-kDa uterine protein (P8) in the cow. P8 was purified, digested to yield internal peptides, and partia lly sequenced to determine identity. Two internal peptides had 100% (1 3-mer) and 92% (12-mer) amino acid sequence identity with bovine granu locyte chemotactic protein-2 (bGCP-2). Bovine GCP-2 is an alpha-chemok ine that acts primarily as a potent chemoattractant for granulocyte ce lls of the immune system. A peptide was synthesized based on a region of bGCP-2 that overlapped with a P8 peptide amino acid sequence, coupl ed to keyhole limpet hemocyanin, and used to generate high titer polyc lonal antiserum in sheep. Western blots revealed that bGCP-2 was not r eleased by endometrium from day 14 nonpregnant cows, but was released in response to 25 nM IFN-tau (p < 0.05). Uterine GCP-2 exhibited high affinity to heparin agarose, a characteristic shared by all alpha chem okines. This is the first report describing presence of GCP-2 in the u terine endometrium and regulation by IFN-tau. The regulation of bGCP-2 by IFN-tau may have important implications for cytokine networking in the uterus during pregnancy. Also, the regulation of inflammation and angiogenesis by bGCP-2 working together with other cytokines may be i ntegral to establishing early pregnancy and implantation in the cow.