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The Importance of Differentiating Gelsolin Isoforms

We read with great interest the article by Candiano and colleagues (1), who concluded that interleukin-4 regulates gelsolin secretion in bronchial epithelia and in asthmatic airways. Their conclusions raise several interesting questions as to what role secreted gelsolin may play in airway inflammation. However, we have concerns about the methods used to quantify gelsolin, which would have a direct effect on how the data are interpreted. Two gelsolin isoforms exist: plasma gelsolin and cytoplasmic gelsolin. Plasma gelsolin is the only isoform that is secreted into the extracellular space, and it differs from cytoplasmic gelsolin by the addition of a 25–amino acid peptide at the N-terminus (2). Candiano and colleagues quantified gelsolin levels by Western analysis using a non–isoform-specific gelsolin antibody (GS-2C4), and by real-time PCR using primers that flank an identical sequence shared by both plasma and cytoplasmic gelsolin mRNAs. Furthermore, the functional assays used by Candiano and colleagues do not distinguish the two gelsolin isoforms.

The observed increase of gelsolin protein may have reflected nonspecific release of cytoplasmic gelsolin by damaged cells, and the observed increase of mRNA expression in stimulated bronchial epithelial cells may be due to cytokine-induced cytoskeletal conformational changes that require cytoplasmic gelsolin. Therefore, one cannot conclude that there is increased secretion of plasma gelsolin as a specific response to stimuli based on the presented data. Differentiating plasma and cytoplasmic gelsolins is crucial because the two gelsolin isoforms have vastly different functions (3, 4). The use of a plasma gelsolin–specific antibody and primers that flank unique sequences of plasma gelsolin will clarify whether plasma gelsolin secretion is indeed increased under the experimental conditions described by Candiano and colleagues.

Po-Shun Lee and Aaron Waxman

Harvard Medical School, Boston, Massachusetts

FOOTNOTES

Conflict of Interest Statement: Neither author has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

REFERENCES

1. Candiano G, Bruschi M, Pedemonte N, Caci E, Liberatori S, Bini L, Pellegrini C, Vigano M, O'Connor JB, Lee TH, et al. Gelsolin secretion in interleukin-4–treated bronchial epithelia and in asthmatic airways. Am J Respir Crit Care Med 2005;172:1090–1096.[Abstract/Free Full Text]
2. Kwiatkowski DJ, Stossel TP, Orkin SH, Mole JE, Colten HR, Yin HL. Plasma and cytoplasmic gelsolins are encoded by a single gene and contain a duplicated actin-binding domain. Nature 1986;323:455–458.[CrossRef][Medline]
3. Kwiatkowski DJ. Functions of gelsolin: motility, signaling, apoptosis, cancer. Curr Opin Cell Biol 1999;11:103–108.[CrossRef][Medline]
4. Lee WM, Galbraith RM. The extracellular actin-scavenger system and actin toxicity. N Engl J Med 1992;326:1335–1341.[Medline]

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