Unit:
Τομέας Υγείας - Μητέρας - ΠαιδιούLibrary of the School of Health Sciences
Author:
Koliopanou Aspasia
Dissertation committee:
1. Χρ. Καττάμης,Καθηγητής ,Ιατρική Σχολή, ΕΚΠΑ
2. Αικ. Μεταξωτού ,Καθηγήτρια,Ιατρική Σχολή ,ΕΚΠΑ
3. Γ. Πάγκαλης ,Καθηγητής,Ιατρική Σχολή,ΕΚΠΑ
4. Δ. Καφετζής ,Αναπλ. Καθηγητής,Ιατρική Σχολή,ΕΚΠΑ
5. Ε. Καναβάκης,Αναπλ. Καθηγητής,Ιατρική Σχολή,ΕΚΠΑ
6. Δ. Αναγνωστάκης,Αναπλ. Καθηγητής,Ιατρική Σχολή,ΕΚΠΑ
7. Ε. Μάνδυλα,Επικ. Καθηγήτρια,Ιατρική Σχολή,ΕΚΠΑ
Original Title:
Παραγωγή stress-πρωτεινών (HSP 70) στα φαγοκύτταρα του νεογνού
Translated title:
Induction of HSP70(heat shock 70 protein) in phagocytes of neonates
Summary:
Ιt is now well established that, when cells of different organisms are exposed to a variety of environmental stresses, including high temperature, anoxia, trauma, inflammation etc. induce the expression of a group of highly conserved proteins, known as heat shock proteins (hsp).
The hsp play a vital role in the survival of cells exposed to stress. Particularity, they help cells pre-exposed to a non lethal stress to survive from subsequent exposure to lethal stress (thermotolerance). The most prominent and profoundly investigated member of this protein group is hsp of a molecular weight of about 70kDa (hsp70). The hsp70 provide protection not only against heat shock, but also against a wide range of other stresses. Invading pathogens represent a common and potentially fatal stress for the organism. Recent reports have shown that the induction of hsp70 reduces the mortality rates from sepsis in several animal models. Only a few studies have referred to human cells and particularly to the in vivo expression of hsp70 by peripheral blood cells. None study had been referred to production of hsp70 by neonatal cells. It is known that neonates have increased susceptibility to different stress-conditions (such as sepsis, anoxia etc). The present study was designed to investigate a) whether the neonatal polymorphonuclear (PMNs) have the ability to synthesize hsp70 and b) if this synthesis could protect the neonatal PMNs from stress-conditions like sepsis and anoxia.
In the first part of this research we have studied venous blood PMNs derived from healthy fullterm and from neonates exposed to stress (sepsis, anoxia). PMNs from healthy adults served as controls. Using the method of Western-blotting we have found the following; 1. PMNs of healthy newborns have the ability to synthesize hsp70 and this synthesis is enhanced when PMNs are exposed to an in vitro stress (exposure of PMNs at a temperature of 42°C). Similar results have been obtained from PMNs of adults exposed to the same conditions. 2. PMNs from neonates with sepsis or hypoxia (that are from neonates exposed to an in vivo stress) had spontaneously overexpressed hsp70 and this expression was much higher than that observed from normal neonatal PMNs that have been exposed to an in vitro stress (temperature of 42°C) 3. PMNs of stressed neonates when exposed to an in vitro heat stress (42°C) continue to synthesize high amounts of hsp70, that were higher than the amount of hsp70 produced by PMNs of normal neonates exposed to similar heat stress.
In the second part of this study we have investigated the role of hsp70 on the superoxide (0-2 ) generation from PMNs derived from normal and stressed neonates. It is known that 0-2 is the precursor substance of the bactericidal free radicals. The generation 0-2 was measured by the superoxide dismutase - inhibitable reduction of ferricytochrome C. We have found the following: 1. When PMNs of healthy newborns had been exposed to a heat shock (42°C) the generation of 0-2 was temporarily inhibited. This is in aggreement with the notion that cells under stress exhibit a repression of their function. However, the preexposure of these neonatal PMNs to a heat shock prevented the inhibition of O- 2 generation during a challenge of a second heat shock. This finding suggests that the neonatal PMNs acquired thermotolerance, as do the PMNs from adults. 2. The 0-2 generation from PMNs of stressed neonates is inhibited and the amount of 0-2 generated is significantly lower than that generated by healthy neonatal PMNs exposed to a heat shock. The 0-2 genaration from the PMNs of stressed neonates was not reestablished after a high temperature exposure in spite of the high production of hsp70 by these cells.
Our results suggest that neonatal PMNs have the ability to synthesize hsp70. However, the hsp70 synthesis cannot protect the normal bactericidal function of the PMNs of stressed neonates and consequently their ability to fight against infections. This may be one of the mechanisms that can explain the high susceptibility of newborns to infection and the increased mortality of neonatal infections. Further investigations on the complex neonatal immunological mechanisms and on the complicated PMNs functions are mandatory if we want to confront neonatal infections that represent a potential danger for neonates.
Keywords:
Heat shock ,Heat shock proteins,Polymorphonuclear,Thermotolerance, Sepsis,Hypoxia,Neonate,Adult,Superoxide, Formyl-peptide
Number of references:
269
