Inflammation
an overview
Hal Hawkins, Ph.D.,M.D.
Fundamentals of Inflammation Course, BBSC 6210
June 25, 2012
Vasodilation and vascular leakage
Cellular:
recruitment
activation
functions
tissue Injury
» Tumor – edema due to plasma leakage
» Rubor – dilation of arterioles and
engorgement of microvasculature
» Calor – increased local temperature
» Dolor –probably due to stretching and
prostaglandins
MARGINATION
ADHERENCE
EMIGRATION AND CHEMOTAXIS
The tongue of the frog
provides an opportunity to
see the microcirculation
and the movements of
neutrophils.
OBSERVATIONS OF
COHNHEIM (1882)
“With the slowing of blood flow in the dilated
venules leukocytes appear in the marginal stream
and tend to stick to the vessel walls. At first the
leukocytes stick momentarily and are then
displaced to be washed away by the blood
stream.“
“As they begin to adhere more closely some are
pushed slowly along by the blood stream,
becoming flattened and elongated in the
direction of the flow so that they have the
appearance of blobs of jelly being pushed along
over a sticky surface.”
more COHNHEIM:
more COHNHEIM:
“Gradually some of the cells adhere more firmly
until even a relatively swift stream of plasma and
red corpuscles cannot dislodge them.
With an adequate injury some of the leukocytes
sticking to the wall begin to make their way
through it by active movements, taking 2 to 12
minutes to do so. “
Will this link work?
http://www.youtube.com/watch?v=WEGGMaRX8f0
Armond Goldman’s discovery of neutrophil integrins
Armond Goldman’s
discovery of
integrins
» http://www.youtube.com/watch?v=9wxK6oLA5
oc
And another one
in color!
» http://www.youtube.com/watch?v=DMvixApKz
Ks
And a third in
diagram form
(from Marchesi and Florey)
» Receptors (complement, IgG, etc.)
» PAF (platelet activating factor)
» Phospholipase 
Inositol triphosphate  Ca++ release
Diacylglycerol  Protein kinase C
http://www.youtube.com/watch?v=ZUUfdP87Ssg
» Complement fragment C5a
» Bacterial formylated peptides
» Arachidonic acid products,
e.g. Leukotriene B4
» Cytokines called chemokines, e.g. IL-8
»
PHAGOCYTOSIS
» FUSION OF GRANULES
» BACTERIAL KILLING
» O2-, superoxide
»
»
»
»
»
H2O2, peroxide
HOCl, hypochlorous acid 
OH•, hydroxyl radical
Acid hydrolases (enzymes)
Bactericidal proteins, defensins,
lactoferrin, lysozyme
Pneumonia
» Plasma proteases, e.g. complement
» Vasoactive amines, e.g. histamine
» Platelet-activating factor PAF
» Arachidonic acid metabolites, e.g.
prostaglandin E3
» Reactive oxygen and nitrogen species
» Cytokines and chemokines, e.g. IL-8
» Neuropeptides and endothelin
» Products of arachidonic acid metabolism
» Potent vasodilators/vasoconstrictors
» Cyclo-oxygenase (COX), needed for
prostaglandin synthesis, is inhibited by
aspirin and selective COX2 inhibitors
including the notorious Vioxx
» Important in fever and pain
» Lipoxygenase leads to leukotrienes,
proinflammatory lipids active in asthma
» O2-, superoxide
» H2O2, peroxide
» HOCl, hypochlorous acid
» OH•, hydroxyl radical
» ONOO-, peroxynitrite
(all reactive oxygen and nitrogen
species)
» Lysosomal neutral hydrolases
» Follows emigration and phagocytosis
» Minimizes tissue injury
» DELAY:
˃ GM-CSF G-CSF
˃ LPS, IL-1, IL-2
˃ IFN-gamma
» STIMULATE:
˃ IL-6
˃ Phagocytosis
˃ Oxidative burst
Neutrophil apoptosis is the key
to prevention of tissue injury.
» Cellular contents may not be released
» Clearance by macrophages stimulates
activation of macrophages to secrete
factors favoring wound healing
Recognition of Pathogen Activated Molecular
Pathways (PAMPs) including Toll Like Receptors
(TLRs) and Damage Activated Molecular Pathways
(DAMPs) (together sometimes called Alarmins).
TLRs stimulate release of multiple pro-inflammatory
peptides.
DAMPs lead to assembly of inflammasomes, activation
of caspase-1, and production of IL-1beta.