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Chemotaxis
- Clinical approaches
Dr. habil. Kőhidai László
2011.
Chemotaxis and infections (1)

Acute skin lesions
cytokine release IL-8
TNF ill. IL-6 are NOT released !

Pseudomonas aeruginosa - formation of biofilms
Klebsiella pneumoniae
- chemotactic activity is
decreased

Burellosis
- chemotactic and phagocytotic
activity of cells decreased
(6 months follow-up study)
Chemotaxis in infections (2)
Helicobacter pylori
-
gastric ulcer
porin 30kD
rapid effect
decreased chemotaxis
3h incubation
TNF
18h incubation
g-IF, GM-CSF,
IL-8, IL-3, IL-4
Chemotaxis and infections (3)
AIDS
HIV reservoirs
cells: monocyte, macrophage
organ: CNS, lung, periph.blood, liver
(The time of replication cycle of virus differes in the
different cells – it is different from lymphocyte)
Cell-physiological functions damaged:
cytokine (chkemokine) synthesis
chemotaxis
phagocytosis
2 mths
chtx.
-19%
phagocyt. -6%
4 yrs
-32%
-18%
Diseases influencing physiological
chemotactic responsiveness (1)
Atherosclerosis
LDL-ox
chemotaxis (monocyte)
cytokine secretion
thrombocyte aggregation
LDL-gly
Amyloidosis
LDL-gly
Amyloid deposits
chr. haemodialysis
b-2-microglobulin
chemotaxis
(monocyte)
TNF IL-1 IL-6
(macrophage)
Diseases influencing physiological
chemotactic responsiveness (2)
Glycogen storage diseases
chemotaxis
Ca2+
O-
+ G-CSF
Cystic fibrosis
lung - LTB4
sputum - IL-8
bacterial infections are
frequent
chemotaxis decreased
Ca2+ norm.
O- norm.
Aut. rec. 7q31
BUT
effect of LTB4 and IL-8
on chemotaxis
is inverse
? receptor down-regulation ? number of IL-8 rec. is 1/3 of normal
(22.000/cell)
Diseases influencing physiological
chemotactic responsiveness (3)
Lung sarcoidosis and fibrosis
levels of MCP-1 and IL-8
are increased
Kartagener syndrome
influx of
neutrophils and monocytes
dynein defficiency
decreased chemotaxis
Diseases influencing physiological
chemotactic responsiveness (4)
Rheumatoid arthritis
chronic inflammation
IL-8
increased chemotaxis
VEGF
(administration of IL-8 can mimic R.A. in experiments)
Asthma bronchiale paroxismal constriction of airways
basophils
increased chemotaxis
biogenic amines are released
Primer inflammations (1)
Peritonitis
- ATP levels in lymphocytes - decreased
chemotactic activity - decreased
- in macrophages chemokinetic activity
expressed – induced by MIP-1
Uveitis
(inflammation of the middle layer of the eye)
chemotaxis is CD11/CD18-dependent
Periodontitis
TNF ands IL-1 levels of sera are increased
IL-1 increases chemotaxis of neutrophils
and the reabsorption of bones
Primer inflammations (2)
Periodontitis
levels of TNF and IL-1 in sera are increased
neutrophil chemotais
IL-1
bone reabsorption
PGE1
inhibits development of inflammation
IGF, FGF, PDGF
chemotaxis
proliferation
differentiation
+ regeneration of osteoblasts
Neutrophil defect of newborns
1 - 8 days
chemotaxis - decreased
13 - 14 days
chemotaxis - normalized
1 - 2 day
chemokinetic act. - normal
after 3rd day
chemotactic act. - decreased
REASON:
- low level expression of CD11 integrin
- low level expression of L selectin
Diseases of circulatory system (1)
Circulatory diseases of the heart
Ischemic heart diseases – transient or lasting occlusion
of coronary
vascular
smooth
muscle
chemoattractants:
fibrinogen (free) - chemotx.
fibrinogen (bound) - haptotax.
Diseases of circulatory system (2)
Reperfusion
Release of chemoattractants is detectable
in the early stage of reperfusion
Invasion of neutrophils guided
by E selectins
Diseases of circulatory system (3)
Peripherial blood vessels
Angiogenesis
proliferation
chemotaxis
morphogenesis
Thrombospondin 1 (TSP1):
inhibits chemotaxis and morphogenesis
Reperfusion
-strats 24h after a min. 3 hrs occlusion
- chemotaxis of PMN cells
Blood vessels in brain
- ischemia results release of FGF
- starts chemotaxis, mitosis, differentiation and
angiogenesis
Diabetes
- increased chemokinetic activity of PMN
- antidiabeticums used in therapy can
decrease the chemokinetic activity
Primer hypothyreosis
- bacterial infections are frequent
- cell adhesion is increased
- chemokinetic activity is decreased
Sclerosis multiplex
- bacterial infections are frequent
- decreased cell adhesion
chemotaxis
phagocytosis
bactericid effects
Hodgkin-disease
decreased chemotaxis
TGFb
Psoriasis
monocyte
macrophage
adhezion
chemotaxis
Edema in lungs,
pmeumothorax(PTX)
increased levels of IL-8 and LTB4
Tumours
Melanoma
Myeloma
endothelin-1 (ET-1)
perivascular chemokinetic effect
production of fMLP-like, chemotactic factor
Human leukemia
expression of MAC-1 inegrin
Therapy
retinoic acid
b-4-integrin expression is decreased
chemotaxis decreased chemoinvasion decreased
(132-2)
(231-28)
Toxic diseases (1)
Alcohol

acute:
3h
Kupffer cells
neutrophil
fMLF rec.
(K=65.000)
24 h
chtx.
2-3 x
120.000
increased
further
200.000
(even 30mM ethanol is effective !!!)

chronic: phagocyte disfunction
Nicotine
- TNF and IL-6 levels are decreased
- IL-8 level is increased
-function of phagocyte function
(macrophages) is affected
Toxic diseases (2)
Quarz, ozone, NO2
quarz
ozone
NO2
Asbestos
chemotaxis decreased, TNF-level increased
TNF-level increased
chemotaxis decreased, TNF-level decreased
IL-1
TNFa
IL-8
Chtx. increased
Methyl~ Hg, Si-lactate
release of reactive oxygen radicals
decreased neutrophil chemotaxis
Mutagenes (benzpyren, 12-dimethyl benzantracen)
increased chemotaxis and chemoinvasiveness
BUT
Hypnosis
X
Chemotaxis