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Related Experiment Videos

Acidosis activates complement system in vitro

M Emeis1, J Sonntag, C Willam

  • 1Department of Neonatology, Charité, Virchow-Hospital, Humboldt-University Berlin, Germany.

Mediators of Inflammation
|February 2, 1999
PubMed
Summary

Acidosis, not lactate, triggers the activation of complement components C3 and C5, leading to anaphylatoxin formation. This study clarifies the direct role of acidosis in immune response activation.

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Area of Science:

  • Immunology
  • Biochemistry
  • Physiology

Background:

  • Acidosis is a condition characterized by an imbalance in the body's acid-base levels.
  • Anaphylatoxins, such as C3a and C5a, are potent mediators of inflammatory and immune responses.
  • The specific role of different types of acidosis in anaphylatoxin formation remains incompletely understood.

Purpose of the Study:

  • To investigate the in vitro effects of metabolic and respiratory acidosis on the formation of anaphylatoxins C3a and C5a.
  • To determine whether acidosis itself or specific acidifying agents (e.g., lactic acid) are responsible for complement activation.

Main Methods:

  • In vitro incubation of heparinized human blood samples (N=12) under various acidosis conditions.
  • Induction of metabolic acidosis using hydrochloric acid or lactic acid.

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  • Induction of respiratory acidosis by altering CO2 levels.
  • Measurement of C3a and C5a levels using appropriate assays.

    • Main Results:

    • Metabolic acidosis (pH 7.0) induced by hydrochloric acid or lactic acid significantly increased C3a and C5a formation compared to controls (p=0.002).
    • Respiratory acidosis also led to significant activation of C3a (p=0.007) and C5a (p=0.003).
    • In respiratory-compensated metabolic acidosis (pH 7.37), C3a and C5a levels were not significantly increased.

    Conclusions:

    • Acidosis, irrespective of its metabolic or respiratory origin, is a direct trigger for the activation of complement components C3 and C5.
    • Lactate itself does not appear to be the trigger for complement activation; rather, the acidic environment is the causative factor.
    • These findings highlight the significant impact of acid-base balance on the innate immune system and anaphylatoxin generation.