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Eur Respir J 2005; 25:1128-1129
Copyright ©ERS Journals Ltd 2005

The immune response to resistive breathing

N. M. Siafakas1 and I. Mitrouska2

1 Medical School, University of Crete, and 2 University General Hospital of Heraklion, Heraklion, Crete, Greece

To the Editors:

The excellent review by Vassilakopoulos et al. 1 discusses in detail the immune response to resistive breathing. The authors report the systemic effects of resistive breathing (cytokines in plasma), as well as the effects of resistive loads on the respiratory muscles (diaphragm).

To the extent that resistive breathing is a potent stimulus for upregulation of cytokines involved in the process of angiogenesis, a review dealing with the immune response to resistive breathing may present the angiogenetic response as well.

Exercise training induces a series of adaptive responses in the cardiovascular and skeletal muscular system, including myofibrillar protein changes, increased activity of oxidative and glycolytic enzymes, and an increased number of capillaries. Such changes in the capillary bed of skeletal muscles in athletes have been detected since the mid 1970s 2, 3. Since then, angiogenesis has been studied extensively and found to be an extremely complex process involving, among others, the dissolution of the extra cellular matrix underlying endothelium, cell migration and endothelial cell proliferation 4, 5. Specific growth factors and predominantly vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and transforming growth factor (TGF)-b1 were found to regulate the angiogenic response to a variety of stimuli 4. A single bout of exercise increases the mRNA levels for the previously mentioned factors 6. Recent data have shown that acute exercise upregulates the mRNA expression, while there is a graded response in the expression of mRNA of this angiogenic factor with the metabolic stress. Furthermore, it is demonstrated that mRNA for VEGF and bFGF in the diaphragm of rats rises significantly as a result of active increased ventilation due to hypoxia and/or hypercapnia, while no changes in mRNA levels were observed in paralysed, mechanically ventilated animals at similar arterial blood gases and ventilation levels 7, 8. However, there is evidence that resistive breathing upregulates mRNA for VEGF, but not for bFGF and TGF-b1 9.

Therefore, angiogenesis, as a result of loading of the respiratory system, is an important part of the integrated immune response to resistive breathing.

REFERENCES

  1. Vassilakopoulos T, Roussos C, Zakynthinos S. The immune response to resistive breathing. Eur Respir J 2004;24:1033–1043.[Abstract/Free Full Text]
  2. Andersen P, Henriksson J. Capillary supply of the quadriceps femoris muscle of man: adaptive response to exercise. J Physiol 1977;270:677–690.[Abstract/Free Full Text]
  3. Andersen P, Henriksson J. Training induced changes in the subgroups of human type II skeletal muscle fibres. Acta Physiol Scand 1977;99:123–125.[ISI][Medline] [Order article via Infotrieve]
  4. Hudlicka O, Brown M, Egginton S. Angiogenesis in skeletal and cardiac muscle. Physiol Rev 1992;72:369–417.[Free Full Text]
  5. Booth FW, Thomason DB. Molecular and cellular adaptation of muscle in response to exercise: perspectives of various models. Physiol Rev 1991;71:541–585.[Free Full Text]
  6. Breen EC, Johnson EC, Wagner H, Tseng HM, Sung LA, Wagner PD. Angiogenic growth factor mRNA responses in muscle to a single bout of exercise. J Appl Physiol 1996;81:355–361.[Abstract/Free Full Text]
  7. Roca J, Gavin TP, Jordan M, et al. Angiogenic growth factor mRNA responses to passive and contraction-induced hyperperfusion in skeletal muscle. J Appl Physiol 1998;85:1142–1149.[Abstract/Free Full Text]
  8. Siafakas NM, Jordan M, Wagner N, Breen EC, Benoit H, Wagner PD. Diaphragmatic angiogenic growth factor mRNA responses to increased ventilation caused by hypoxia and hypercapnia. Eur Respir J 2001;17:681–687.[Abstract/Free Full Text]
  9. Jordan MWH, Breen EC, Benoit H, Wagner PD, Siafakas NM. Effect of resistive loading on angiogenic growth factor mRNA of the respiratory muscles. Am J Respir Crit Care Med 1998;157:A669




This Article
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