Peter Newburger, MD University of Massachusetts Medical School

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