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Role of CD146 in Detection of Apoptotic Circulating Endothelial Cells in Obstructive Sleep Apnea

We appreciate the comments regarding our recently published article (1). We concur that CD146 is not only expressed by circulating endothelial cells (CECs) but also by other cell types, such as activated T cells, smooth muscle cells, follicular dendritic cells, trophoblasts, and melanoma cells. Therefore, any approach using CD146 to identify endothelial cells among other circulating blood cells has to recognize the potential expression of this marker on a subset of activated T lymphocytes as reported by Pickl and colleagues (2) and more recently by Elshal and colleagues (3).

We would like to point out that our study is not intended to address the current debate on the ideal CEC marker. In the absence of a clear consensus on phenotypic identification (4), a combination of different criteria is used to define CECs. In our study, only selectively gated CD146 cells that were negative for T-cell, B-cell, neutrophilic, and monocytic pan-lineage markers were considered as CECs by flow cytometric analysis. In addition, Elshal and colleagues (3) showed that 1% or less of mononuclear cells expressed CD45 CD146 in healthy volunteers. While this fraction is thought to be increased in patients with OSA, Dyugovskaya and coworkers (5) found no significant percentage change in T lymphocytes expressing CD8, CD16, and CD56 between patients with OSA and control subjects.

Based on these findings, it is unlikely that our observations of reduced apoptotic CEC post–continuous positive airway pressure therapy could be attributed to a subset of activated T lymphocytes. Moving forward, we hope that our results promote further investigation between the role of cytokines and various hematopoietic cells in patients with OSA.

Ali El Solh

State University of New York at Buffalo, Buffalo, New York

FOOTNOTES

Conflict of Interest Statement: A.E.S. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

REFERENCES

1. El Solh AA, Akinnusi ME, Baddoura FH, Mankowski CR. Endothelial cell apoptosis in obstructive sleep apnea: a link to endothelial dysfunction. Am J Respir Crit Care Med 2007;175:1186–1191.[Abstract/Free Full Text]
2. Pickl WF, Majdic O, Fischer GF, Petzelbauer P, Fae I, Waclavicek M, Stockl J, Scheinecker C, Vidicki T, Aschauer H, et al. MUC18/MCAM (CD146), an activation antigen of human T lymphocytes. J Immunol 1997;158:2107–2115.[Abstract]
3. Elshal MF, Khan SS, Takahashi Y, Solomon MA, McCoy JP Jr. CD146 (Mel-CAM), an adhesion marker of endothelial cells, is a novel marker of lymphocyte subset activation in normal peripheral blood. Blood 2005;106:2923–2924.[Free Full Text]
4. Goon PK, Boos CJ, Stonelake PS, Blann AD, Lip GY. Detection and quantification of mature circulating endothelial cells using flow cytometry and immunomagnetic beads: a methodological comparison. Thromb Haemost 2006;96:45–52.[Medline]
5. Dyugovskaya L, Lavie P, Lavie L. Phenotypic and functional characterization of blood T cells in sleep apnea. Am J Respir Crit Care Med 2003;168:242–249.[Abstract/Free Full Text]

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