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Chemotaxis - Clinical approaches

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

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Chemotaxis - Clinical approaches

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  1. Chemotaxis - Clinical approaches Dr. habil. Kőhidai László 2011.

  2. Chemotaxis and infections (1) • Acute skin lesions cytokine release IL-8 • TNF ill. IL-6 are NOT released ! • Pseudomonas aeruginosa - formation ofbiofilms • 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. chemotaxis Ca2+ O- chemotaxis decreased Ca2+ norm. O- norm. + G-CSF Diseases influencing physiological chemotactic responsiveness (2) Glycogen storage diseases bacterial infections are frequent 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-8influx of are increased neutrophils and monocytes Kartagener syndromedynein defficiency decreased chemotaxis

  8. increased chemotaxis basophils biogenic amines are released 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

  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 PGE1inhibits development of inflammation chemotaxis proliferation differentiation IGF, FGF, PDGF + regeneration of osteoblasts

  11. 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

  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. Peripherial blood vessels proliferation chemotaxis morphogenesis Angiogenesis Diseases of circulatory system (3) 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. TGFb monocytemacrophage Psoriasis adhezion chemotaxis Hodgkin-disease decreased chemotaxis Edema in lungs, pmeumothorax(PTX) increased levels of IL-8 and LTB4

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

  18. Toxic diseases (1) Alcohol 3 h 24 h • acute: Kupffer cells chtx. increased • neutrophil 2-3 x further • fMLF rec. 120.000 200.000 • (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. IL-1 IL-8 Chtx. increased TNFa Toxic diseases (2) Quarz, ozone, NO2 quarz chemotaxis decreased, TNF-level increased ozone TNF-level increased NO2 chemotaxisdecreased, TNF-level decreased Asbestos 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

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