Essential Role for Platelets in Organ Injury and Inflammation in Resuscitated Hemorrhagic Shock

Abstract

Platelets are known to contribute to ischemia/reperfusion in several organs, but their role in inflammation and organ injury after hemorrhagic shock (HS) has not been examined. To address this issue, we rendered mice thrombocytopenic (20% of normal platelet count) by treatment with pOp3, a rat monoclonal antibody against platelet glycoprotein Ibalpha, 24 h before subjecting them to either a standard HS or sham protocol. Liver apoptosis increased 3- to 5-fold (P<0.05), and focal liver necrosis increased 11-fold (P<0.01) in placebo-treated shock mice compared with sham; these increased indices of liver injury were completely prevented by pOp3 pretreatment. Neutrophils infiltrating the liver increased nearly 3-fold in placebo-treated shock mice versus sham (P<0.05); this shock-induced increase in neutrophil infiltration was also eliminated by pretreatment with pOp3. Alveolar cross-sectional area, used to histologically assess interstitial lung edema and cellular infiltration, was reduced by 25% in pOp3-treated shock mice versus placebo-treated shock mice (P<0.05). Similar to the results in liver, pOp3 pretreatment decreased neutrophil infiltration in the lung after HS. Thus, platelets contribute to the inflammatory injuries of the liver and lung after HS, in part, perhaps by facilitating neutrophil infiltration into tissues.

The Hepatic Microcirculation: Mechanistic Contributions and Therapeutic Targets in Liver Injury and Repair

“…Thus adherent platelets might significantly prolong life span of leukocytes and, thus, their capacity for oxidative burst and release of proteolytic substances. Accordingly, interference with platelet sequestration by inhibition of PSGL-1 and GP1b, P-selectin deficiency, or induction of thrombocytopenia induces protection in normo-and hypothermic postischemic, endotoxemic, and cholestatic liver injury (163,168,453,526,822,829,918). Hereby, endothelial, but not platelet, P-selectin expression seems critical for postischemic platelet-endothelial cell interactions (379).…”

Platelets Enhance Endothelial Adhesiveness in High Tidal Volume Ventilation

“…High tidal volume ventilation (HV) causes lung inflammation (1)(2)(3), thereby contributing to morbidity and mortality in acute lung injury (ALI) (4,5) Since it is increasingly evident that activated platelets determine ALI (6)(7)(8), the role of platelets in HV-induced lung inflammation requires further understanding, especially in the context of platelet-endothelial cell (EC) interactions. The EC role is likely to be significant, since inflammatory EC responses, including those relevant to barrier regulation and the expression of proinflammatory receptors, are critical in the development of ALI (4,5,9,10).…”

The Role of Platelets in Viral Hemorrhagic Fevers

“…As platelets contain many vasoactive substances, such as serotonin, platelet factor 4 and histamine, their degranulation can down-regulate platelet production [104], and disrupt endothelial function. This platelet-endothelial interaction is also important in the pathogenesis of shock [98,102,[105][106][107][108]. In sepsis, neutrophil binding to platelets leads to platelet [93], and adhered platelets support neutrophil adhesion [109].…”

“…Platelets play an important role in septic shock [81,90,[96][97][98][99][100][101][102]. Activation of platelets leads to degranulation and adhesion to leukocytes and endothelial cells.…”