A New Role of Acute Phase Proteins: Local Production Is an Ancient, General Stress-Response System of Mammalian Cells

Abstract

The prevailing general view of acute-phase proteins (APPs) is that they are produced by the liver in response to the stress of the body as part of a systemic acute-phase response. We demonstrated a coordinated, local production of these proteins upon cell stress by the stressed cells. The local, stress-induced APP production has been demonstrated in different tissues (kidney, breast cancer) and with different stressors (hypoxia, fibrosis and electromagnetic heat). Thus, this local acute-phase response (APR) seems to be a universal mechanism. APP production is an ancient defense mechanism observed in nematodes and fruit flies as well. Local APP production at the tissue level is also supported by sporadic literature data for single proteins; however, the complex, coordinated, local appearance of this stress response has been first demonstrated only recently. Although a number of literature data are available for the local production of single acute-phase proteins, their interpretation as a local, coordinated stress response is new. A better understanding of the role of APPs in cellular stress response may also be of diagnostic/prognostic and therapeutic significance.

Protective effects of dietary grape against atopic dermatitis-like skin lesions in NC/NgaTndCrlj mice

“…However, the role of most of the APPs are not known in AD. APR signaling is responsible for activating the system in response to stimuli such as infections, trauma, and tissue infarction, to limit the amount of tissue damage ( 84 ). APR activity is mediated by pyrogenic cytokines, such as IL-6, TNFα, and IFNγ ( 85 ).…”

The Association of Acute Phase Proteins in Stress and Inflammation-Induced T2D

“…APPs, which are markers of inflammation, have been closely associated with T2D as their serum levels are elevated in T2D patients [ 44 , 92 , 150 , 154 , 155 , 156 ]. These include PAI-1, SAA, and CRP, which all play different roles in response to inflammation such as opsonization, activating the complement system modulating the host’s immune response, and aiding in repairing damaged tissue thereby establishing homeostasis during the APR [ 210 ].…”

Patients with Bacterial Sepsis Are Heterogeneous with Regard to Their Systemic Lipidomic Profiles

“…In our present study, we have investigated the systemic lipidomic profiles of patients with bacterial sepsis, and we observed that sepsis patients are characterized by a specific profile at the time of diagnosis. This profile may reflect an effect of local infection and inflammation on distant organs similar to the acute phase reaction [ 13 , 14 ], development of organ dysfunctions [ 3 ] and/or the metabolic status/requirements of the inflammatory cells at the site of infection. Thus, the molecular mechanisms behind this metabolic profile are probably diverse, and in our detailed analyses of the metabolomics data we focused on the Sepsis-3/Sepsis-2 comparison and bacteremia analyses (but not infection site and bacterial Gram-positive/negative classification) because both of these factors show highly significant associations to disease severity.…”

“…As stated above, the observed differences in serum levels of lysophosphatidylcholines, sphingolipids and certain triacylglycerols are probably caused by diverse mechanisms, including the local inflammation itself, the effect of the local inflammation on distant organs similar to the acute phase reaction and organ dysfunctions/failures due to sepsis [ 3 , 13 , 14 ]. However, immunoregulatory effects on these systemic levels due to their availability for the immunocompetent/inflammatory cells at the local inflammatory site may also be important.…”

“…According to the definition and staging of sepsis, this is also a systemic reaction/complication in distant organs to an (initially) localized infection [ 1 , 2 , 3 ]. Sepsis-associated systemic metabolic modulations detected in serum/plasma may thus reflect an effect of local infection and inflammation on distant organs similar to the acute phase reaction [ 13 , 14 ], development of organ dysfunctions [ 3 ] and/or the metabolic status/requirements of inflammatory cells at the site of infection. In this context, we therefore investigated the lipidomic profiles of patients with bacterial sepsis at the time of hospital admission, prior to the start of antibiotic and supportive treatment, and we had a main focus on structurally defined lipid metabolite subsets rather than on the levels of individual metabolites.…”