CD16⁺Monocyte Subsets Are Increased in Large Abdominal Aortic Aneurysms and Are Differentially Related with Circulating and Cell-Associated Biochemical and Inflammatory Biomarkers

Abstract

Proinflammatory components are present in abdominal aortic aneurysm (AAA). Circulating monocytes display heterogeneity, and three subsets have been identified, based on the differential expression for CD14 and CD16 receptors: CD14+CD16-, classical, CD14+CD16+, intermediate and CD14dimCD16+, non-classical monocytes. Increased proinflammatory CD16+monocytes with high expression of CD143 are present in CKD patients. D-dimer is increased in AAA patients, and might contribute to the pro-inflammatory response associated to circulating monocytes. We aimed to investigate the frequency of CD14+CD16+, CD14dimCD16+monocytes and monocyte CD143 expression in AAA patients, and their relationship with D-dimer, eGFR and other inflammatory parameters. Blood from 74 AAA patients and 30 healthy controls was analyzed to determine the frequency of CD14+, CD16+, CD14dimCD16+monocytes and the monocyte CD143 expression by means of flow-cytometry. AAA patients had expanded CD16+SUPsets (CD14+CD16+: 7.66 ± 0.31% vs 5.42 ± 0.27%; CD14dimCD16+: 7.43 ± 0.48% vs 5.54 ± 0.38%, AAA vs controls, mean ± SE, both p<0.05). CD14+CD16+cells were associated to D-dimer and age, and to reduced eGFR. CD14dimCD16+cells were associated to uric acid, surface CD143, and reduced count of total leukocytes and neutrophils. Within AAA patients, the two CD16+supsets and the monocyte CD143 expression display different relationships with D-dimer, parameters of renal function and circulating biochemical and inflammatory biomarkers.

Hemoglobin induces monocyte recruitment and CD163-macrophage polarization in abdominal aortic aneurysm

“…The majority of monocytes express cell surface CD14 (CD14 + CD16 − ), whereas a minor subpopulation of monocytes also express the cell surface activation marker CD16, identifying them as more mature than the CD14 + CD16 − subpopulation. In agreement with previous studies [27], our data show that human peripheral blood monocyte subsets might be differentially distributed in AAA patients. Thus, CD14 ++ CD16 + monocytes were expanded, whereas proportion of CD14 ++ CD16 − monocytes was decreased in AAA-patients as compared with healthy individuals.…”

“…CD16 + monocytes are thought to be the precursors of tissue-resident macrophages [21][22][23][24][25]. The CD16 + subset of monocytes increases significantly in chronic phagocytic conditions, such as atherosclerosis and AAA [26,27]. CD16 + consist of two subsets with distinct phenotypic and functional properties, namely, CD14 ++ CD16 + and CD14 + CD16 + cells.…”

Inflammatory Cell Phenotypes in AAAs

“…89 Recent studies showed that patients with AAAs have increased levels of CD14 + CD16 + monocytes compared to control patients, suggesting these monocytes may be associated with the chronic inflammatory process of AAA. 90 CD16, a low affinity Fc receptor for IgG antibodies involved in antibody-dependent cytotoxicity, is also associated with an M1 macrophage polarization. 91 Experimental aneurysm models indicated that CD14 deletion reduced inflammatory cell infiltration therefore reducing AAA incidence.…”

Inflammatory Mediators in Abdominal Aortic Aneurysms

“…ECM breakdown is a recruiter of monocytes, and the use of a monoclonal antibody has been shown to decrease this iniltration and prevent further ECM degradation [31]. Furthermore, the monocytes have demonstrated CD14 and CD16 cell surface marker positivity, and this patern is associated with M1 macrophage activation [32].…”