Saturday, February 9, 2008

Neutrophil Chemotaxis- Neutrophil Function

If you read anything about Shwachman-Diamond Syndrome, chances are you'll read about poor neutrophil function or defective neutrophil chemotaxis.

What is neutrophil chemotaxis?

Chemotaxis can be defined as the ability of the neutrophils to move to the site of infection. If neutrophils are unable to migrate (move) to the site of infection, a person is said to have a neutrophil chemotaxis defect. Medical literature suggests that most Shwachman-Diamond Syndrome patients have some level of neutrophil chemotaxis defect. For instance, my two SDS boys were tested at two different labs (using two different techniques) and were found to have neutrophil chemotaxis dysfunction. In one of the studies, only 17% of J's neutrophils moved toward the bacteria, while 33% of S's moved toward the bacteria. The control that was sent along with their samples had 100% of her neutrophils move toward the bacteria.

Neutrophils also produce enzymes that kill invading bacteria, which also helps neutrophils to kill these foreign pathogens.

The following comes from a diagnostics textbook 5th edition:

Normal neutrophils--the body's primary defense against bacterial invasion--engulf and destroy bacteria and foreign particles by a process known as phagocytosis. In patients who have repeated bacterial infections, neutrophil function tests may reveal the inability of neutrophils to kill a target bacteria or to migrate to the bacterial site (chemotaxis).

Neutrophil killing ability can be evaluated by the nitroblue tetrazolium (NBT) test, which relies on neutrophil generation of bactericidal enzymes and toxins during killing. This action results in increased oxygen consumption and glucose metabolism, which reduces colorless NBT to blue formazan. The reduced dye is then extracted with pyridine and measured photometrically; the level of reduction indicates phagocytic activity.

Neutrophil killing activity can also be evaluated by noting the neutrophils' chemiluminescence--ability to emit light. After a neutrophil phagocytizes a microorganism, oxygen-containing substances form within the phagocytic vacuoles. As the cell is stimulated, it emits light in proportion to the amount of oxygen-containing substances that are formed, providing an indirect measurement of phagocytosis.

Chemotaxis can be assessed in vitro by placing bacteria in the lower half of a two-part chamber and phagocytic neutrophils in the upper half. After incubation, migrating cells are counted microscopically and compared to standard values."