@article{oai:rakuno.repo.nii.ac.jp:00002474, author = {Chou, Wen K and Yu, Ting C and Chen, Shuen E and Peh, Ho C and Liu, Wen B and Chen, Ming T and Nagahata, Hajime and Chang, Chai J}, issue = {4}, journal = {Journal of Dairy Research}, month = {Nov}, note = {Article, Interactions between inflammatory cytokines and plasminogen (Pg) activation system on immune cells are yet to be established. In previous studies we reported a somatic cell-associated elevation of proteolytic activity in mammary secretion of drying-off goats and cows. The purposes of the present study were to examine the role of TNF-α in polymorphonuclear neutrophil (PMN)-associated Pg activation, and the significance of this activation pathway for overall plasmin (Pm) activity in mammary secretion of drying-off cows. Results of experiments in vitro showed that the spontaneous Pg activation observed on fresh preparations of bovine blood PMN was completely blocked by anti bovine TNF-α antibody, and was further up-regulated by exogenous bovine TNF-α. Monitoring the parameters of mammary secretion of drying-off cows revealed that both somatic cell counts and differential PMN ratio was significantly elevated at weeks 1, 2 and 3 of milk stasis. Nevertheless, specific activity of soluble Pm in mammary secretion increased and the level of 17-kDa TNF-α decreased immediately following milk stasis. Iimmunoblotting revealed that although both 26-kDa pro-TNF-α and 17-kDa TNF-α were consistently present in somatic cells of mammary secretion collected at weeks 0, 1, 2 and 3 of milk stasis, only 26-kDa pro-TNF-α was present in somatic cells of milk during lactation. In-vitro assay indicated that cell-free mammary secretion of drying-off cows exerted no Pg activation bioactivity towards bovine blood PMN. Altogether, the current study suggests the existence of an active TNF-α-Pg-Pm autocrine/paracrine loop on the massively infiltrated PMN inside udders of drying-off cows, which involves extensive binding and internalization of 17-kDa TNF-α on PMN and consequently activation of Pg, resulting in high Pm activity and low 17-kDa TNF-α level in mammary secretion. These coordinated mechanisms may play a role in the defence of drying-off mammary gland.}, pages = {459--468}, title = {TNFα-mediated plasminogen activation on neutrophils is involved in the high plasmin activity in mammary secretion of drying-off cows}, volume = {76}, year = {2009} }