PubMed HealthSearch

PubMed · 7583160

The acute-phase response.

Abstract

Inflammation and tissue injury elicit profound changes in the concentrations of several plasma proteins. These proteins are predominantly synthesized in the liver and named acute-phase proteins. The regulatory mechanisms that control this response are highly complex and include the release of various mediators affecting specific subsets of acute-phase genes. Individual mediators can either synergistically enhance or inhibit the effects of other mediators. Binding of mediators to their respective receptors on hepatocytes and transduction of this signal induce changes in acute-phase protein gene expression that are primarily regulated on a transcriptional level. However, under certain conditions post-transcriptional mechanisms may also be involved in this process. Although some acute-phase proteins have been shown to minimize tissue damage, as well as to participate in hemostasis, tissue repair, and regeneration in response to injury, the actual in vivo functions of several acute-phase reactants remain speculative. Measurements of acute-phase protein plasma concentrations can be of diagnostic or prognostic value under certain clinical conditions. Further characterization of the regulatory mechanisms that govern the acute-phase response in vivo could lead to the development of new therapeutic strategies aimed at improving the organism's integrated response to injury.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

B H Pannen, J L Robotham. 1995. The acute-phase response.. https://pubmed.ncbi.nlm.nih.gov/7583160/

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

STAT3 mediates the survival signal in oncogenic ras-transfected intestinal epithelial cells.

The oncogenic ras mutation is a common and critical step in gastrointestinal carcinogenesis. In a previous study, we demonstrated that oncogenic ras activated the EGF-related peptide autocrine loop and that the apoptosis resistance observed in the oncogenic ras-stimulated cell (IEC-ras cell) was dependent on this activated EGF-related peptide autocrine loop. STATs (signal transducers and activators of transcription), first identified as intracellular signal transducers stimulated by cytokines, are known to also be activated by EGF. However, the role of STATs in the survival signal of IEC-ras cells is not clear. In the present study, we demonstrate that STAT3 is constitutively activated in ras-stimulated cells and that STAT3 activation is considerably suppressed by the EGF-specific receptor kinase inhibitor AG 1478. We also show that disruption of the STAT3 pathway by introduction of a dominant-negative STAT3 mutant abolishes the apoptosis resistance against UVC and MMC treatment observed in IEC-ras cells without affecting proliferation. Moreover, the expression of Bcl-2 and Bcl-xL, apoptosis-suppressive proteins, is reduced in dominant-negative STAT3-transfected cells. Thus, STAT3 appears to be an important mediator of the antiapoptotic signal in IEC-ras cells.

Acute-Phase Proteins

A synthetic lipopolysaccharide-binding peptide based on amino acids 27-39 of serum amyloid P component inhibits lipopolysaccharide-induced responses in human blood.

LPS-binding proteins in plasma play an important role in modifying LPS toxicity. Significant properties have already been attributed to the LPS-binding protein (LBP). It accelerates LPS toxicity as well as incorporation into high-density lipoproteins, leading to neutralization of LPS in serum. A search for other LPS-binding components in serum, using LPS-coated magnetic beads, revealed a new LPS-binding protein. N-terminal microsequencing identified this protein as serum amyloid P component (SAP). Purified SAP bound to smooth and rough types of LPS via the lipid A part. SAP inhibited the binding of FITC-labeled ReLPS (LPS from Salmonella minnesota strain R595) to human monocytes and the ReLPS-induced priming of the oxidative burst of human neutrophils only in the presence of low concentrations of LBP. In search for the LPS binding site of SAP, we found that pep27-39, a 13-mer peptide consisting of amino acids 27-39 of SAP, competitively inhibited the binding of LPS to SAP. In addition, pep27-39 significantly inhibited ReLPS-induced responses in phagocytes in the presence of serum, as well as in human whole blood. Carboxamidomethylated pep27-39 showed an even more pronounced reduction of the ReLPS-induced priming of phagocytes in human blood. Performing gel filtration of FITC-labeled ReLPS incubated with soluble CD14, we showed that SAP could not prevent binding of LPS to soluble CD14, in contrast to pep27-39. The ability of pep27-39 to antagonize specifically the effects of LPS in the complex environment of human blood suggests that pep27-39 may be a novel therapeutic agent in the treatment of gram-negative sepsis.

Acute-Phase Proteins

Identification and cloning of a glucan- and lipopolysaccharide-binding protein from Eisenia foetida earthworm involved in the activation of prophenoloxidase cascade.

Coelomic fluid of Eisenia foetida earthworms contains a 42-kDa protein named coelomic cytolytic factor 1 (CCF-1) that was described previously to be involved in cytolytic, opsonizing, and hemolytic properties of the coelomic fluid. Cloning and sequencing of CCF-1 reveal significant homology with the putative catalytic region of beta-1,3- and beta-1,3-1,4-glucanases. CCF-1 also displays homology with coagulation factor G from Limulus polyphemus and with Gram-negative bacteria-binding protein of Bombyx mori silkworm, two proteins involved in invertebrate defense mechanisms. We show that CCF-1 efficiently binds both beta-1,3-glucan and lipopolysaccharide. Moreover, CCF-1 participates in the activation of prophenoloxidase cascade via recognition of yeast and Gram-negative bacteria cell wall components. These results suggest that the 42-kDa CCF-1 protein of E. foetida coelomic fluid likely plays a role in the protection of earthworms against microbes.

Acute-Phase Proteins