PMID- 12427127
OWN - NLM
STAT- MEDLINE
DCOM- 20030523
LR  - 20131121
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 62
IP  - 6
DP  - 2002 Dec
TI  - Dual effects of Escherichia coli alpha-hemolysin on rat renal proximal tubule 
      cells.
PG  - 2035-42
AB  - BACKGROUND: alpha-Hemolysin (HlyA) producing Escherichia coli is a common cause 
      of pyelonephritis and subsequent renal scarring. Recent studies have suggested 
      that toxin secreted from HlyA E. coli may not only have a lytic effect, but also 
      may activate a calcium signaling pathway in renal tubule cells. A dose dependent 
      study was performed on the interaction between HlyA E. coli secretions and rat 
      renal proximal tubule (PT) cells with regards to calcium signaling and cell 
      morphology. The site of interaction between HlyA secretion and PT cells was 
      examined by using an antagonist to a common binding motif in bacterial proteins. 
      METHODS: Supernatant from an overnight culture of HlyA was freshly prepared for 
      each experiment. Renal PT cells from infant rats were cultured for three days and 
      exposed for 30 minutes to four hours to supernatant or purified HlyA. Effects on 
      cell morphology were studied semiquantitatively with light microscopy. 
      Intracellular calcium was measured ratiometrically in the presence or absence of 
      drugs. RESULTS: Renal PT cells incubated with low doses of HlyA supernatant 
      responded within five minutes with calcium oscillations. Morphology appeared 
      unchanged after four hours of incubation. In contrast, high doses of HlyA caused 
      a sustained increase in intracellular calcium and majority of cells were lysed 
      within four hours. Calcium oscillations caused by lower doses of HlyA supernatant 
      were highly regular and slow in the 10 to 12 minute range. Oscillations were 
      abolished by 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX), indicating that HlyA 
      is interacting with a QPB/LAOBP-motif. CONCLUSION: HlyA secreted from 
      uropathogenic E. coli exerts a dual action on renal PT cells. Sublytical 
      concentrations induce a response that may serve as a host defense, while high 
      concentrations cause irreversible cell damage. The data emphasize the importance 
      of high diuresis in urinary tract infection.
FAU - Laestadius, Asa
AU  - Laestadius A
AD  - Department of Woman and Child Health, and Microbiology and Tumor Biology Centre, 
      Karolinska Institutet, Stockholm, Sweden. asa.laestadius@ks.se
FAU - Richter-Dahlfors, Agneta
AU  - Richter-Dahlfors A
FAU - Aperia, Anita
AU  - Aperia A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Escherichia coli Proteins)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Hemolysin Proteins)
RN  - 0 (Hlya protein, E coli)
RN  - 0 (Nicotinic Antagonists)
RN  - 0 (Receptors, AMPA)
RN  - 6EE945D3OK (Mecamylamine)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
RN  - 6OTE87SCCW (6-Cyano-7-nitroquinoxaline-2,3-dione)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - 6-Cyano-7-nitroquinoxaline-2,3-dione/pharmacology
MH  - Animals
MH  - Calcium/metabolism
MH  - Calcium Signaling/drug effects
MH  - Cells, Cultured
MH  - Dizocilpine Maleate/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Escherichia coli Proteins/*toxicity
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - Gene Expression
MH  - Hemolysin Proteins/*toxicity
MH  - Kidney Tubules, Proximal/cytology/*drug effects/metabolism
MH  - Mecamylamine/pharmacology
MH  - Nicotinic Antagonists/pharmacology
MH  - Pyelonephritis/pathology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, AMPA/genetics
EDAT- 2002/11/13 04:00
MHDA- 2003/05/24 05:00
CRDT- 2002/11/13 04:00
PHST- 2002/11/13 04:00 [pubmed]
PHST- 2003/05/24 05:00 [medline]
PHST- 2002/11/13 04:00 [entrez]
AID - S0085-2538(15)48770-8 [pii]
AID - 10.1046/j.1523-1755.2002.00661.x [doi]
PST - ppublish
SO  - Kidney Int. 2002 Dec;62(6):2035-42. doi: 10.1046/j.1523-1755.2002.00661.x.