Classification of acute-phase reactants
Depending on their reaction to the inflammatory process, proteins are divided into positive (concentration in the blood increases) and negative (concentration drops).
Main groups of reactants:
- Proteases (positive only). Trypsinogen, elastase, cathepsins, matrix metalloproteinases. Their activation is required for the formation of inflammatory mediators and killer functions.
- Protease inhibitors (positive only). These include α2-macroglobulin and α1-antitrypsin. They balance proteases, protecting tissues from excessive damage.
- Complement components. Positive: C1 inhibitor, factors C2, C3, C4, factor B. Negative: properdin.
- Clotting factors. Positive: fibrinogen, plasminogen, prothrombin, factor VIII. Negative: factor XII.
- Transport and other proteins. Positive: fibronectin, procalcitonin, transport proteins (haptoglobin, transferrin), whose role changes qualitatively during inflammation. Negative: albumin, low-density (LDL) and very low-density lipoproteins (VLDL).
Pentraxins — major acute-phase proteins
The pentraxin family most fully reflects the properties of acute-phase proteins. In the first 24 hours of inflammation, their level can increase up to 10,000-fold. The pentraxin molecule is ring-shaped and consists of five identical globular subunits bound non-covalently.
The spatial structure of the monomer core is formed by anti-parallel β-sheets and is called the "jelly roll" (jelly roll). Meanwhile, the ligand-binding sites of each of the five domains hold two calcium ions (Ca²⁺) each.
The family is divided into two major groups:
- Short pentraxins (C-reactive protein, serum amyloid P component). Consist solely of classical pentraxin domains. Synthesized in hepatocytes under the influence of the cytokine IL-6.
- Long pentraxins (PTX3 protein). Have an additional N-terminal domain of a different structure. Produced by myeloid cells (macrophages, dendritic cells), epithelial cells, and fibroblasts in response to Toll-like receptor (TLR) stimulation and cytokines (IL-1β, TNFα).
Functions in innate immunity
Pentraxins act as soluble pattern-recognition receptors (PRRs) for pathogen-associated molecular patterns (PAMPs). They bind to a huge number of molecules: bacterial polysaccharides, DNA, complement components, and extracellular matrix components.
Their main functions:
- Role of "proto-antibodies". Prior to the production of true antibodies, they opsonize microorganisms to facilitate phagocytosis.
- Complement activation. Triggered through interaction with the C1q factor.
- Regulation of inflammation. Pentraxins activate neutrophils and macrophages, stimulate chemotaxis, and regulate cytokine production. They have a high affinity for FcγRI and FcγRII cell receptors.
- Homeostasis. Involved in the elimination of apoptotic cells, remodeling of the extracellular matrix upon injury, and even the control of fertility.
Briefly: answers to topical questions
Which proteins are negative acute-phase reactants?
Negative acute-phase reactants are proteins whose concentration decreases during inflammation. This group includes:
- Properdin — belongs to the complement system components.
- Factor XII — acts as a blood clotting factor.
- Albumin — is a transport protein.
- Low-density lipoproteins (LDL).
- Very low-density lipoproteins (VLDL).
Which blood clotting factors act as positive acute-phase proteins?
The following blood clotting factors act as positive acute-phase proteins:
- Fibrinogen
- Prothrombin
- Factor VIII
- Plasminogen
Their concentration increases during inflammation.
What is the normal baseline concentration of C-reactive protein in blood serum?
The normal baseline concentration of C-reactive protein in blood serum is less than 1 µg/mL. During the development of an inflammatory process, this indicator can increase sharply by 1,000 times, reaching values of 1–2 mg/mL. The peak concentration of this short pentraxin is reached 6–8 hours after the induction of inflammation, and levels practically normalize by the end of the first week.
What are the clinical indications for determining procalcitonin levels?
Clinical indications for determining procalcitonin levels include suspected bacterial flora invasion and the development of sepsis. The test is ordered in the following situations:
- Severe COVID-19 — for early risk assessment and exclusion of bacterial coinfection in patients with severe and critically severe disease courses.
- Suspected sepsis — the marker is used for the diagnosis and prognosis of sepsis, as well as in suspected bacterial infection.
- Infective endocarditis — acts as a marker in the etiological diagnosis of valvular heart disease.
To remember the main negative acute-phase reactants, use the mnemonic: PRO-perdin, AL-bumin, Factor XII (and do not forget lipoproteins LDL/VLDL).
Class and exam questions
Why is C-reactive protein (CRP) named that way?
The name is associated with its ability to specifically recognize and bind the C-polysaccharide of the bacterium Streptococcus pneumoniae.
What is the difference in the synthesis induction of short and long pentraxins?
Short pentraxins (CRP) are induced predominantly by interleukin-6, while long pentraxins (PTX3) are induced through Toll-like receptor stimulation and pro-inflammatory cytokines IL-1β and TNFα.
How does the concentration of PTX3 protein change during inflammation?
Its serum concentration rises from a baseline of 25 ng/mL to 200–800 ng/mL.
What else to study on this topic
- Mechanism of complement system activation via the C1q factor
- Spatial structure of the "jelly roll" (jelly roll)
- Features of calcium ion binding in pentraxin domains
- Involvement of acute-phase proteins in extracellular matrix remodeling
- Interaction of acute-phase reactants with FcγRI and FcγRII receptors
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