Adaptive and Maladaptive Mechanisms of Cellular Priming

Abstract

ObjectiveThe mechanisms of cellular priming resulting in both adaptive and maladaptive responses to subsequent injury and strategies for manipulating this priming to constructive therapeutic advantage are explored.Background Data A cell is prepared or educated by an initial insult (priming stimulus). Investigations in both laboratory animals and humans indicate that cells, organs, and perhaps even whole patients respond differently to a proximal second insult ("second hit") by virtue of this prior environmental history. The opportunity to achieve the primed state appears to be conserved across almost all cell types. The initial stimulus transmits a message to the cellular machinery that influences the cell's response to a subsequent challenge. This response may result in an exaggerated inflammatory response in the case of the neutrophil (an often maladaptive process) or an improved tolerance to injury by the myocyte (adaptive response). Our global hypothesis is that cellular priming is a conserved, receptor-dependent process that invokes common intracellular targets across multiple cell types. We further postulate that these targets create a language based on the transient phosphorylation and dephosphorylation of intracellular enzymes that is therapeutically accessible.

Activation of RAGE induces elevated O2− generation by mononuclear phagocytes in diabetes

“…Cellular priming is usually a conserved, receptor-dependent process [37]. To confirm that activation of RAGE causes the priming, an in vitro blocking of this receptor with anti-RAGE antibody was used to pretreat the cells before adding the ligand S100B.…”

Tolerance to Shock: An Exploration of Mechanism

“…Alterations in the immune response that occur after an initial insult are central to the concept of "priming" or cellular reprogramming. [1][2][3] The changes in immune function that occur during priming can be either detrimental or beneficial to the host organism when it is exposed to a subsequent systemic insult. It is possible to condition animals by prior sublethal hemorrhage (SLH) such that they tolerate what should be a subsequent lethal hemorrhage.…”

Neutrophil Priming State Predicts Capillary Leak after Gut Ischemia in Rats

“…Neutrophil adherence is determined in part by expression of the ␤2 integrins. CD18 is the ␤2 integrin or transmembrane portion of the neutrophil adhesion receptor complex responsible for firm attachment to endothelial cells in postcapillary venules [10,13,14]. Neutrophil number, activity, and adhesion are considered important factors in determining the neutrophil priming state or ability to evoke distant organ failure after local tissue injury.…”