Transcript My Favorite Cell: Neutrophil production and function

OurNeutrophils:
How I came to know and love them
Peter Newburger, MD
University of Massachusetts Medical School
Cell:
OurFavorite
My
Neutrophil function
Neutrophils – blood smear
Neutrophil – electron micrograph
Neutrophils – scanning EM
Neutrophil in real time
Ilya Ilyich Mechnikov and the thorn in the starfish (1883)
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
Mechnikov: Macrophages and “microphages” eat bacteria (1887)
Mechnikov: Macrophages and “microphages”
exit from blood vessels and eat bacteria (1887)
Recruitment of Neutrophils During Inflammation
1. Free flow
2. Rolling
Endothelial cells
Bacteria
Opsonins
3. Firm Adhesion
Chemotaxis
5. 4.
Phagocytosis/Bacterial
Transmigration
killing
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
Superoxide-generating
system
2O2
2O2_
Extracellular space
or
phagosome
Heme
2e_
FAD
NADPH
Cytoplasm
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