Transcriptional Control of Complement Activation in an Exercise Model of Chronic Fatigue Syndrome – Source: Molecular Medicine, Nov 16, 2008

[Note: Full text of this article is available free in PubMed Central. C4a and MASP2 are two of the nine genes whose expression the researchers measured after exertion in CFS patients vs healthy controls. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2583111]

Complement activation resulting in significant increase of C4a split product may be a marker of post-exertional malaise in chronic fatigue syndrome (CFS) subjects. This study was focused to identify the transcriptional control that may contribute to the increased C4a in CFS subjects post-exercise.

Differential expression of genes in the classical and lectin pathways were evaluated in peripheral blood mononuclear cells (PBMCs) using quantitative reverse transcription PCR. Calibrated expression values were normalized to internal (peptidylpropyl isomerase B [PPIB]) or external (ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit [rbcL]) reference genes or geometric mean (GM) of genes ribosomal protein, large, P0 (RPLP0) and phosphoglycerate kinase 1 (PGK1).

All nine genes tested, except mannose-binding lectin 2 (MBL2), were expressed in PBMCs.

At 1 hr post-exercise, C4, mannan-binding lectin serine protease 2 (MASP2) and ficolin 1(FCN1 ) transcripts were detected at higher levels (>/= 2-fold) in at least 50% (4 out of 8) of CFS subjects that increased to 88% (7 out of 8) CFS subjects when subjects with over-expression of either C4 or MASP2 were combined.

Only increase in MASP2 transcript was statistically significant [PPIB, p=0.001; GM, p=0.047; rbcL, p=0.045]). This may be due to the significant but transient down-regulation of MASP2 in control subjects (PPIB, p = 0.023; rbcL, p = 0.027).

By 6 hrs post-exercise, MASP2 expression was similar in both groups.

In conclusion:
• Lectin pathway responded to exercise differentially between CFS and control subjects.
• MASP2 down-regulation may act as an anti-inflammatory acute-phase response in healthy subjects,
• Whereas its elevated level may account for increased C4a and inflammation mediated post-exertional malaise in CFS subjects.

Source: Molecular Medicine, Nov 16, 2008 E-pub ahead of print. PMID: 19015737, Sorensen B, Jones JF, Vernon SD, Rajeevan MS. Division of Viral and Rickettsial Diseases, National Center for Zoonotic, Vector-borne and Enteric Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; Department of Integrative Biology, University of Colorado at Boulder; CFIDS Association of America, Charlotte, North Carolina, USA. [E-mail: mor4@cdc.gov]

 

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