Macrophages antimicrobial and cytotoxic activities

Antimicrobicia! & cytotoxic substances produced by activated macrophages can destroy phagocytosed microorganisms.

Mediators of antimicrobial and cytotoxic activity of macrophages and neutrophils

Oxygen-dependent killing

Oxygen-independent killing

Reactive oxygen intermediates

O2.- (Superoxide anion)

OH- (Hydroxide radicals)

H2O2 (Hydrogm peroxide)

ClO- (Hypochlorite anion)

Defensins

Tumor necrosis factor -alpha

(macrophage only)

Lysozyme

Hydrolytie enzymes

Reactive nitrogen intermediates

NO (nitric oxide)

NO2 (nitrogen dioxide)

HNO2 (nitrous oxide)

  

Others

NH2Cl (monochloramine)

  

A) Oxygen-dependent killing mechanism:

  • Activated phagocytes produce a number of "Reactive Oxygen Intermediates (ROIs)" & "reactive nitrogen intermediates" that have potent antimicrobial activity. 
  • During phagocytosis, a metabolic process known as the "Respiratory Burst" occurs in activated macrophages.
  • Due to the respiratory burst, membrane - bound enzyme "Oxidase" will activate, that catalyzes the reduction of oxygen to superoxide anion (powerful oxidizing agent), a reactive oxygen intermediate & hydroxyl radicals &H2O2.
  • As the lysosomes fuses with the phagosomes, the activity of "Myeloperoxidase" produces hypochlorite from hydrogen peroxide and chloride ions.
  • Hypochlorite, the active agent of household bleach, is toxic to ingested microbes.
  • When the macrophages are activated with bacterial cell wall components. The T-cell derived cytokine (IFN-γ), they begin to express high levels of “Nitric Oxide synthatase"(NOS), an enzyme that oxidizes L-arginine to yield L-Citrulline & nitric oxide (NO), a gas.

L-Arginine + O2 + NADPH -> NO + L-Citrulline +NADP+

  • No has potent anti-microbial activity.

B) Oxygen-independent killing mechanism:

  • Activated macrophages also synthesize 'lysozyme' and various hydrolytic enzymes whose degradative activities do not require Oxygen.
  • The activated macrophages produce a group of anti­microbials cytotoxic peptides, commonly known as "Defensin", these Molecules are cystine- rich cationic peptides containing 29-35 Amino acids residues.
  • The defensin is circularized protein.
  • The peptide form ion-permeable channel in bacterial cell membrane.

Intracellular pathogens:

  • Some microorganism can survive & multiply within pathogens include:
    • Listeria monocytogenes
    • Salmonella typhimurium
    • Neisseria gonorrhoeae &
    • Mycobacterium aviutn
    • Mycobacteriura tuberculosis
    • Mycobacterium leprea
    • Brucella abortus &
    • Candida albicans
  • Some intracellular pathogens prevent the fusion of lysosomes with phagosome and proliferate with in phagosomes.

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