Changes in the monocytic subsets CD14(dim)CD16(+) and CD14(++)CD16(-) in chronic systolic heart failure patients

Offer Amir, Ilia Spivak, Idit Lavi, Michal Amit Rahat, Offer Amir, Ilia Spivak, Idit Lavi, Michal Amit Rahat

Abstract

Different monocytic subsets are important in inflammation and tissue remodelling, but although heart failure (HF) is associated with local and systemic inflammation, their roles in HF are yet unknown. We recruited 59 chronic systolic HF patients (aged 58 ± 13 years, 45 males and 14 females) and 29 age-matched controls with no pervious heart disease. Compared to the controls, we found no change in the distribution of the CD14(+)CD16(+) monocytic subset, whereas the classical CD14(++)CD16(-) subset was decreased by 11% (P < 0.001), and the nonclassical CD14(dim)CD16(+) subset was expanded by 4% (P < 0.001) in HF patients and was inversely associated with severe HF (P = 0.015), as assessed by increased end-diastolic dimension (EDD). Compared to the control group, serum TNFα, IL-1β, IL-10, and IL-13 levels were significantly elevated in the HF patients. Specifically, IL-13 levels were positively correlated to the CD1CD14(dim)CD16(+) monocytic subset (r = 0.277, P = 0.017), and intracellular staining of IL-13 demonstrated that some of these monocytes produce the cytokine in HF patients, but not in the controls. We suggest that the inverse association between EDD values and the expansion of CD14(dim)CD16(+) monocytes that can produce IL-13 could be explained as a measure to counterbalance adverse remodelling, which is a central process in HF.

Figures

Figure 1
Figure 1
Characterization of monocyte subsets in HF patients and controls. (a) Representative flow cytometry dot plots of monocyte subsets in a healthy control and an HF patient, including the median values of each subset. Monocytes were gated by their side and forward scattering, and (b) their percentage from total blood leukocytes was determined; monocytes that were positive for HLA-DR expression were separated into three subsets according to their expression of CD14 and CD16, and their percentage of the total monocytes was determined in (c) CD14+CD16+ monocytes (gated R2 in (a), the green subpopulation), (d) CD14++CD16− monocytes (gated R1 in (a), the red subpopulation), and (e) CD14dimCD16+ monocytes (gated R3 in (a), the blue subpopulation).
Figure 2
Figure 2
Production of IL-13 by each of the monocyte subsets. (a) Representative flow cytometry histograms of IL-13 producing monocyte subsets in a healthy control and an HF patient. Each of the three monocytes subsets was gated as described in Figure 1, and their respective ability to express IL-13 was evaluated by intracellular staining for the cytokine (n = 5). Grey histogram, isotype control for IL-13; red histogram, the CD14++CD16− classical subset; green histogram, the CD14+CD16+ subset; blue histogram, the CD14dimCD16+ nonclassical subset. (b) Their percentage (median values) from the CD14dimCD16+ monocytes was determined.

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