Neutrophils
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Introduction
Neutrophils are the most abundant white cell in the blood, numbering 2-8x109/L. They are important mediators of the innate immune system and are a key component of inflammatory responses to bacteria and other threats.
- online video: neutrophil chasing bacteria
- online video: a posse of neutrophils migrating
Neutrophil Functions
Neutrophils are potent phagocytic cells, eating perceived threats to the body. They kill organisms using a respiratory burst.
Primary granules contain lysozyme, hydrolytic enzymes (proteases, phospholipases, elastases, and collagenases), myeloperoxidase
Secondary granules: defensins, lysosyme.
About Neutrophils
Neutrophils have segmented nuclei, with 3-4 segments connected by tapering chromatin strands. Primary granules are large and purple, with secondary granules being small and orange/pink. They are approximately 14 um in diameter.
Neutrophils mature over 5-7 days in the bone marrow and circulate for 7-10 hours before migrating into tissues at sites of local inflammation. There they die within 48 hours. Up to 1010 neutrophils are therefore produced per day through granulopoiesis. Rates increase perhaps tenfold during acute inflammation.
Meylocytes, metamyelocytes, bands, neutrophils
like sending in new recruits, then army cadets, then 12 year olds with baseball bats. a bad situation
Neutrophil Activation and Extravasation
During an inflammatory response, various cytokines and other molecules act on local blood vessels to induce endothelial activation.
The process of neutrophil extravasation involves four steps: rolling, activation, adhesion, and transendothelial migration.
During inflammation, endothelial adhesion molecules such as E- and P- selectin are expressed and bind to neutrophil ligands, causing rolling.
Neutrophil activation occurs by the action of various chemoattractants, produced by endothelial cells or in the connective tissue.
They include:
- chemokines such IL-8 or MIP-1b, PAF
- complement split products such as C3a or C5a
- various peptides produced by bacterial proteins.
These signals are mediated by GPCR pathways. Neutrophil activation induces changes in adhesion molecule avidity and expression, acusing firm adhesion to the endothelial wall.
Migration next occurs, followed by chemotaxis and migration through extracellular tissues.
Leukocyte margination, induced by stasis, facilitates rolling and adhesion to activated endothelium, mediated by PSGL-1 and integrin binding to selectins and ICAM-1 on the endothelium. Chemokines cause an increase in avidity of leukocyte adhesion molecules. Over time, the endothelium becomes lined with white blood cells in a process called pavementing.
Problems with Neutrophils
Neutropenia is a decreased number of neutrophils.
Febrile neutropenia is a serious condition where the body is under attack and less able to defend itself.
Chronic granulomatous disease (CGD) results from a deficiency of phagocyte NADPH oxidase. This leads to dysfunctional killing of bacteria and fungi, and patients suffer recurrent infection.
Resources and References
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