Peter Newburger, MDUniversity of Massachusetts Medical School
OurNeutrophils:How I came to know and love them
Our Favorite Cell:Neutrophil functionMy
Neutrophils – blood smear
Neutrophil – electron micrograph
Neutrophils – scanning EM
Neutrophil in real time
One day when the whole family had gone to a circus to see some extraordinary performing apes, I remained alone with my microscope, observing the life in the mobile cells of a transparent star-fish larva, when a new thought suddenly flashed across my brain. It struck me that similar cells might serve in the defence of the organism against intruders. Feeling that there was in this something of surpassing interest, I felt so excited that I began striding up and down the room and even went to the seashore in order to collect my thoughts.I said to myself that, if my supposition was true, a splinter introduced into the body of a star-fish larva, devoid of blood-vessels or of a nervous system, should soon be surrounded by mobile cells as is to be observed in a man who runs a splinter into his finger. This was no sooner said than done.There was a small garden to our dwelling, in which we had a few days previously organised a 'Christmas tree' for the children on a little tangerine tree; I fetched from it a few rose thorns and introduced them at once under the skin of some beautiful star-fish larvae as transparent as water.I was too excited to sleep that night in the expectation of the result of my experiment, and very early the next morning I ascertained that it had fully succeeded.That experiment formed the basis of the phagocyte theory, to the development of which I devoted the next twenty-five years of my life.
— Elie Metchnikoff'Uber die Pathologische Bedeutung der Intracellularen Verduung', Fortschritte der Medizin (1884), 17, 558-569. Trans. Alfred I.
Tauber and Leon Chernyak, Metchnikoff and the Origins of Immunology (1991), 141
Ilya Ilyich Mechnikov and the thorn in the starfish (1883)
Mechnikov: Macrophages and “microphages” eat bacteria (1887)
Mechnikov: Macrophages and “microphages” exit from blood vessels and eat bacteria (1887)
Recruitment of Neutrophils During Inflammation
Bacteria
1. Free flow
Endothelial cells
2. Rolling3. Firm Adhesion
Chemotaxis4. Transmigration5. Phagocytosis/Bacterial killing
Opsonins
Neutrophil rolling and adhesion
Neutrophil rolling and adhesion
Ingestion (phagocytosis)and Degranulation
Neutrophil granule contents
Oxidative killing
O2־ + O2־ → H2O2 + O2
hydrogen peroxide
H2O2 + Cl ־ → HOCl + H2O
hypochlorous acid
H2O2
Superoxide-generating system
2O2 2O2_
Heme
FAD
2e_
Extracellular space or
phagosome
CytoplasmNADPH
NETs: Neutrophil Extracellular Traps
Bacteria trapped in
NETs
Staph aureus
E. coli
Neutrophils also cause inflammation and tissue damage
Normal aortic valve
Neutrophils also cause inflammation and tissue damage
Aortic valve after Staph infection
Neutrophils also cause inflammation and tissue damage
Arthritis in man … … and his best friend