Overview Topics

Chemical concentrations and conversions

Molecule Type

 

Molecular weight

Conversion: 1pg/ml converts to

Conversion: 1 nM converts to

Amyloid-Beta

3-4 kD

2.84 x 10 - 4 nM

 3520 pg/ml

IL-1 beta

17 kD

5.85 x 10 - 5 nM

 17100 pg/ml

IL 6

26 kD

3.83 x 10 - 5 nM

 26110 pg/ml

TNF-alpha

17kD

5.85 x 10 - 5 nM

17100 pg/ml

Pharmacological specificity of IL-1alpha (100 pM) binding to
mouse hippocampus (from [4]).

Peptide

 

Biological activity [U*/mg]

IL-1alpha

3.1 X 107

IL-1beta

2.0 X 107

IL-1beta+

1.0 X 106

Human TNF

8.0 X 102

Rat/human CRF

0.0

* 1U activity = the amount required for half-maximal induction of
cell proliferation (see [4]).

** These conversions are done as follows:

1 [pg/ml] x [1000 ml / L] x [10 - 12 g / pg] x [ 1 kDa / (1.67 x 10 - 21) gm] x [ 1 molecule / (weight in kDa) ]

x [1 M / 6.02 x 10 23 molecules] x [10 9 nM / M] = [ 9.95 x 10 - 4 / (mol weight) ] nM


Chemical secretion rates and concentrations

 

Molecule Type

 

Molecular weight

Typical Concentration

Ref

Amyloid-Beta

3-4 kD

0-100 nM

 

IL-1 beta

17 kD

2 pg/ml (control)

12 pg/ml (AD brain)

[5]

IL 6

26 kD

0.2 pg/ml (control)

0.6 pg/ml (AD brain)

[5]

TNF-alpha

17kD

18.8 pg/ml (control)

300 pg/ml (AD brain)

[1]

Note: Sometimes international activity units, U, are used. For IL-6, 1 ng/ml = 100 U/ml.


Cytokine secretion amounts and rates

 

(A) Microglia

Type

 

Amounts secreted by microglia in response to LPS

Comments

Ref

IL-1 beta

300 pg

(inside cells)

0.2 x10 6 cells for 4 hrs

[2]

IL 6

2000 pg

0.2 x10 6 cells for 4 hrs

[2]

TNF-alpha

400 pg

0.2 x10 6 cells for 4 hrs

[2]

 

 

Type

 

Rate secreted per microglial cell in response to LPS

Comments

IL-1 beta

0.366 nM / min

Computed as shown below

IL 6

1.6 nM / min

"

TNF-alpha

0.488 nM /min

"

Computed as a local concentration change assuming that cell secretes substance into an adjoining volume, V = (10 microns) 3 . To convert the pg in this volume into pg/ml we do the following:

1 [pg / V] x [V / (10 micron)3] x ([104 micron / cm])3 x [1 cm3 / ml] = 109 pg/ml.

If there are n cells secreting for a time duration d hrs, and using the conversion factor c from above, the concentration change in the given volume per minute will be:

1 [(pg/V) / (n cells)] x [109 (pg/ml) / (pg/V)] x [ 1 / (d hr)] x [c nM/(pg/ml) ] x [ 1hr / 60 min ]

= (109/60 ) c / (d n) nM/min per cell


(B) Astrocytes

Type

 

Amounts secreted by astrocytes in response to IL-1beta

Comments

Ref

IL 6

250 pg

0.2 x10 6 cells for 8 hrs

[2]

TNF-alpha

80 pg

0.2 x10 6 cells for 8 hrs

[2]

 

 

Type

 

Rate secreted per astrocyte cell in response to IL-1beta

Comments

IL 6

0.100 nM / min

Computed as shown above

TNF-alpha

0.049 nM /min

"

 


(C) Monocytes

 

Type

 

Amount secreted by monocytes in response to A-beta

Comments

Ref

IL 6

0-150 pg

5 x10 6 cells for 48 hrs

[3]

TNF-alpha

0-1500 pg

5 x10 6 cells for 48 hrs

[3]

  

Type

 

Secretion rate per monocyte cell in response to A-beta

Comments

IL 6

0-0.399 x 10 - 3 nM / min

Computed as above

TNF-alpha

0-6.09 x 10 - 3 nM / min

 

 


References

  1. Benveniste EN. Tang LP. Law RM. Differential regulation of astrocyte TNF-alpha expression by the cytokines TGF-beta, IL-6 and IL-10.International Journal of Developmental Neuroscience 13(3-4):341-9, 1995 Jun-Jul.Abstract

  2. Lee SC, Liu W, Dickson DW, Brosnan CF, Berman J W (1993). Cytokine production by human fetal microglia and astrocytes, differential induction by lipopolysaccharide and IL-1-beta. J Immunol 150(7): 2659-2667.Abstract

  3. Fiala M, Zhang L, Gan X, Sherry B, Taub D, Graves MC, Hama, S, Way D, Weinand M, Witte M, Lorton D, Kuo Y_M, Roher AE (1998). Amyloid-beta induces chemokine secretion and monocyte migration across human blood-brain barrier model. Molec Med 4: 480-489.Abstract
    See more details here.

  4. Takao T. Tracey DE. Mitchell WM. De Souza EB.Interleukin-1 receptors in mouse brain: characterization and neuronal localization. Endocrinology 127(6):3070-8, 1990 Dec.Abstract

  5. Tarkowski E. Blennow K. Wallin A. Tarkowski A.Intracerebral production of tumor necrosis factor-alpha, a local neuroprotective agent, in Alzheimer disease and vascular dementia. Journal of Clinical Immunology. 19(4):223-30, 1999 Jul.Abstract



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