Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

A critical view of monocyte subpopulations in human hypercholesterolemia.

Abstract

We have read with great interest the article by Fadini et al. reporting that circulating monocyteemacrophages (MoMas) show an imbalance toward pro-inflammatory M1 MoMas in patients with hypercholesterolemia and atherosclerosis compared to healthy subjects [1]. Also, non-familiar hypercholesterolemia (NFH) was associated with a more severe M1/M2 MoMas imbalance than familiar hypercholesterolemia (FH). The authors speculated that adverse diet and lifestyle, factors contributing to hypercholesterolemia in NFH, were even more detrimental than genetics for the development of inflammation. No significant differences were observed among groups in the distribution of three monocyte subsets, defined as classical (CD14þþCD16; or Mon1), intermediate (CD14þþCD16þ; or Mon2) and non-classical monocytes (CD14þCD16þ; or Mon3) [1]. Even though the work highlights an important field in atherosclerosis research, we would like to formulate some remarks. Fadini et al. identified the monocyte population solely on physical features, i.e. on a FSC vs. SSC density plot on flow cytometric analysis. Albeit CD68 and CX3CR1 were chosen to selectively gate subsets, no additional pan-monocytic marker was used to distinguish monocytes from other cells such as neutrophils and NK cells. Yet, precise gating of the real total monocyte population is of value when trying to obtain consistent quantitative information of any monocyte subset. For this purpose, approaches that include an extra pan-monocyte marker, such as CD86 or HLA-DR, have been designed [2,3]. Next, optimal discrimination between the intermediate and non-classical monocyte subsets by flowcytometry has been a matter of debate. In his article, Fadini et al. preferred to adhere to a CD14 vs. CD16 plot with rectangular gating.