Thrombin-induced interleukin 1βsynthesis in platelet suspensions: Impact of contaminating leukocytes

Abstract

A controversial discussion as to whether human platelets are capable of regulated protein synthesis has been ongoing for over half a century. A previous study has suggested that human platelets synthesize large amounts of interleukin 1beta (IL-1beta) in response to external cues and in a physiologically significant manner. However, cytokines such as IL-1beta are generally considered to be products of leukocytes and it could not be completely excluded that contaminating leukocytes may have contributed to the IL-1beta results in platelet preparations. It was therefore our intention to investigate whether residual leukocytes had an impact on thrombin-induced IL-1beta synthesis. Using various methods to reduce the level of contaminating leukocytes, we found that IL-1beta production in platelet-rich suspensions is dependent on the presence of leukocytes, as it was decreased by reducing the number of leukocytes. In addition, we found that thrombin-induced IL-1beta synthesis was completely eliminated in leukocyte-free platelet preparations and could be restored by adding leukocytes. IL-1beta synthesis could be detected in platelet suspensions contaminated with at least 1 leukocyte per 10(5) platelets. This study demonstrated that platelets are incapable of synthesizing detectable amounts of IL-1beta on their own. We suggest that any IL-1beta synthesis detected is a by-product of leukocytes contaminating the platelet preparations. Thus, the hypothesis that platelets producing IL-1beta, provide a new link between thrombosis and inflammation needs to be reconsidered.

Comparative evaluation of leukocyte- and platelet-rich plasma and pure platelet-rich plasma for cartilage regeneration

“…reported that chondrocytes from the native cartilage did not participate in the repopulation of the defect, and that the cartilaginous repair appeared to be mediated by the proliferation and differentiation of mesenchymal cells from the bone marrow32. TNF-α was selected as a pro-inflammatory cytokine, and this protein along with IL-1β are key cytokines associated with the catabolic state observed in OA33, and leukocytes are the primary source of inflammatory cytokines such as IL-1 and TNF-α3435363738. L-PRP contained more leukocytes, TNF-α and IL-1β than P-PRP in the present study.…”

Platelet Tissue Factor Synthesis in Type 2 Diabetic Patients Is Resistant to Inhibition by Insulin

“…Some investigators attributed a positive outcome to contamination with monocytes, which have a many-fold–higher translation capacity (22–24). Therefore, we included a purity check in every experiment to demonstrate unequivocally that platelets synthesize TF.…”

Lipopolysaccharide Is a Direct Agonist for Platelet RNA Splicing

“…Thrombin activated platelets move IL-1β to their surface(21, 22) where it participates in juxtacrine stimulation of endothelial cells(21), and they secrete small amounts of mature IL-1β(23) that participates in the inflammatory process. These observations have now been challenged with the suggestion that even low numbers of monocytes in platelet preparations are sufficient to account for thrombin-stimulated IL-1β production(24). Assessing contaminating nucleated cells in platelet preparations is difficult(25) when their abundance needs to be less than one per hundred thousand platelets(24).…”

“…These observations have now been challenged with the suggestion that even low numbers of monocytes in platelet preparations are sufficient to account for thrombin-stimulated IL-1β production(24). Assessing contaminating nucleated cells in platelet preparations is difficult(25) when their abundance needs to be less than one per hundred thousand platelets(24). This is an important topic given that extreme leukoreduction, on the order of 1 leukocyte per million platelets, is a critical issue in platelet transfusion medicine ((26), and references therein).…”