1. Chemotaxis - Clinical approaches
Dr. habil. Kőhidai László
2017.

2. 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)

3. 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

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 4 yrs
chtx. -19% -32%
phagocyt. -6% -18%

5. Diseases influencing physiological chemotactic responsiveness (1)
Atherosclerosis LDL-ox LDL-gly
chemotaxis (monocyte)
cytokine secretion
thrombocyte aggregation
LDL-gly
Amyloidosis Amyloid deposits
chr. haemodialysis b-2-microglobulin
chemotaxis TNF IL-1 IL-6
(monocyte) (macrophage)

6. Diseases influencing physiological chemotactic responsiveness (2)
Glycogen storage diseases bacterial infections are
frequent
chemotaxis
Ca2+ O-
+ G-CSF
chemotaxis decreased
Ca2+ norm.
O- norm.
Cystic fibrosis Aut. rec. 7q31
lung - LTB4 BUT effect of LTB4 and IL-8
sputum - IL-8 on chemotaxis
is inverse
? receptor down-regulation ? number of IL-8 rec. is 1/3 of normal
(22.000/cell)

7. Diseases influencing physiological chemotactic responsiveness (3)
Lung sarcoidosis and fibrosis
levels of MCP-1 and IL influx of
are increased neutrophils and monocytes
Kartagener syndrome dynein defficiency
decreased chemotaxis

8. 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

9. 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

10. 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
chemotaxis
proliferation
differentiation
IGF, FGF, PDGF
+ regeneration of osteoblasts

11. Neutrophil defect of newborns
1 - 8 days chemotaxis - decreased
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

12. 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.

13. Diseases of circulatory system (2)
Reperfusion Release of chemoattractants is detectable
in the early stage of reperfusion
Invasion of neutrophils guided
by E selectins

14. 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

15. - increased chemokinetic activity of PMN
- antidiabeticums used in therapy can
decrease the chemokinetic activity
Diabetes
Primer hypothyreosis
- bacterial infections are frequent
- cell adhesion is increased
- chemokinetic activity is decreased
- bacterial infections are frequent
- decreased cell adhesion
chemotaxis
phagocytosis
bactericid effects
Sclerosis multiplex

16. Hodgkin-disease decreased chemotaxis
Psoriasis
monocyte macrophage
TGFb
adhezion
chemotaxis
Edema in lungs,
pmeumothorax(PTX)
increased levels of IL-8 and LTB4

17. chemoinvasion decreased
Tumours
Melanoma
endothelin-1 (ET-1)
perivascular chemokinetic effect
Myeloma production of fMLP-like, chemotactic factor
Human leukemia expression of MAC-1 inegrin
Therapy
retinoic acid b-4-integrin expression is decreased
chemotaxis decreased
(231-28)
chemoinvasion decreased
(132-2)

18. Toxic diseases (1) Alcohol 3 h 24 h
acute: Kupffer cells chtx. increased
neutrophil 2-3 x further
fMLF rec
(K=65.000)
(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

19. Toxic diseases (2) Quarz, ozone, NO2
quarz chemotaxis decreased, TNF-level increased
ozone TNF-level increased
NO2 chemotaxis decreased, TNF-level decreased
Asbestos
IL-1 IL-8 Chtx. increased
TNFa
Methyl~ Hg, Si-lactate
release of reactive oxygen radicals
decreased neutrophil chemotaxis
Mutagenes (benzpyren, 12-dimethyl benzantracen)
increased chemotaxis and chemoinvasiveness

20. BUT
Hypnosis X
Chemotaxis