Plasmin resulted in increased neutrophil adherence to cultured ovine pulmonary artery endothelial cell monolayers in a concentration-dependent manner (10(-12)-10(-7) M). The adherence response increased fivefold above baseline within 60 min after addition of plasmin (10(-8) M) and the response persisted up to 30 min after removal of plasmin. The neutrophil adherence was mediated by the action of plasmin on neutrophils rather than endothelial cells. The response was the result of an increase in functional activity of CD18 neutrophil cell surface adhesive glycoprotein. Neutrophil adherence was inhibited by pretreatment of neutrophils with MAbs IB4 and 60.3 targeted against the beta chain of the CD18, whereas control isotypic MAb 60.5 against HLA class I antigen had no effect. The plasmin catalytic site was not involved in the response. Lys-plasminogen had reduced adherence-promoting activity relative to plasmin, whereas glu-plasminogen had no effect. Elastase-derived plasminogen fragments corresponding to kringle 1+2+3 and kringle 4 (both of which contained the lysine-binding sites) possessed neutrophil adherence-promoting activities similar to plasmin, whereas miniplasminogen (which contains the catalytic site but no lysine-binding sites) had minimal effect, indicating the involvement of lysine-binding sites in the response. Blocking lysine-binding sites of plasmin and elastase-derived plasminogen fragments with tranexamic acid (IC50 of 5 mM) inhibited neutrophil adherence. A monospecific polyclonal antibody against the lysine-binding sites also reduced the neutrophil adherence-promoting activity of plasmin. The results indicate that plasmin induces neutrophil adherence to the endothelium and that the effect is mediated by lysine-binding sites on plasmin.
S K Lo, T J Ryan, N Gilboa, L Lai, A B Malik
Usage data is cumulative from August 2021 through August 2022.
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.