Neutrophils are granulocytes because they have densely staining granules in their cytoplasm. Because of their oddly shaped nuclei they are also called polymorphonuclear leukocytes.
There are three types of granulocytes which are distinguished by the different staining properties of the
granules:
- neutrophils
- eosinophils
- basophils
Neutrophils
Every day the bone marrow produces millions of new neutrophils. They are mainly involved in the initial phase of an inflammatory response. Neutrophils are recruited into the inflamed tissue in large numbers during an inflammation. Neutrophils are also known as inflammatory cells. Neutrophils have surface receptors for common bacterial constituents and for complement which makes them principal cells that engulf and destroy the invading microorganisms.
Macrophages in tissues when when challenged are triggered to release chemokines which direct the migration of neutrophils to the site of infection. TH17 cells produce distinct cytokines that help to promote responses rich in the recruitment of neutrophils and which are effective in dealing with extracellular bacteria and fungi.
Neutrophils produce alpha-defensins. alpha-defensins are made by processing of an initial propeptide of 90 amino acids to removal of anionic propiece by cellular proteases. This process makes a mature cationic defensin that is stored in the primary granules. The primary granules of neutrophils are specialized membrane enclosed vesicles, rather similar to lysosomes, that contain a number of other antimicrobial agents as well as defensins.
The beta-defensins lack the anionic propiece and are generally produced specifically in response to a challenge. The tetha-defensins arose in the primates, but the single human tetha-defensin gene has been inactivated by a mutation.
Antimicrobial mechanisms
Some of the bactericidal agents produced or released by neutrophils after uptake of microorganisms are listed below. These agents listed are toxic and can act directly in the phagolysosome.
Competitor secretion:
On the site of infection or an immune response, neutrophils secrete a few substances which will sequester/trap few compounds(such as Fe2+ or vitamin B12) this will prevent their growth. Lactoferrin sequesters Fe2+ and vitamin B12-binding protein which binds to vitamin B12 both remove the essential substrate required for bacterial growth.
Lactoferrin binds to lipopolysaccharide of bacterial walls, and the
oxidized iron part of the lactoferrin oxidizes bacteria via formation of
peroxides. This affects the membrane permeability and results in the cell breakdown (lysis).
Reference: Farnaud S, Evans RW (2003). "Lactoferrin—a multifunctional protein with antimicrobial properties". Mol. Immunol. 40 (7): 395–405.
Antimicrobial peptides:
Various anti-microbial peptides are secreted by neutrophils. A few of them are listed below.
a-Defensins (HNP1-4), b-defensin (HBD4), cathelicidin, azurocidin, bacterial permeability inducing protein (BPI), lactoferricin.
Toxic nitrogen oxides and Toxic oxygen-derived products
Nitric oxide (NO): neutrophils are armed with inducible nitric oxide synthase (iNOS). And Superoxide O2-, hydrogen peroxide H2O2, singlet oxygen, hydroxyl radical OH, hypohalite OCl- are some of the reactive oxygen intermediates which help in killing microbes.
Enzymes
Low pH
A low pH of 3.5 - 4.0 is bacteriostatic or bactericidal for various microbes.
- Lysozyme ia an enzymes that damage bacterial cell walls by catalyzing hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in a peptidoglycan.
- Acid hydrolase enzymes such as elastase and other proteases break down proteins and hydrolysis various components of bacterial cell wall.
Low pH
A low pH of 3.5 - 4.0 is bacteriostatic or bactericidal for various microbes.
References:
1. Charles A Janeway, Jr, Paul Travers, Mark Walport, and Mark J Shlomchik; Immunobiology, 5th edition; The Immune System in Health and Disease.
