title: Association between monocyte Fcgamma subclass expression and acute coronary syndrome.
abstract: BACKGROUND: Atherosclerosis lesions contain abundant immunoglobulins complexed with oxidized LDL (OxLDL) that are endocytosed by macrophages to form foam cells. While recent evidence supports a role for the macrophage scavenger receptor pathway in 75-90% of OxLDL uptake, in vitro evidence suggests another potential uptake pathway could involve autoantibody binding to IgG subclass-specific Fc receptors. OBJECTIVE AND METHODS: To address this mechanism from an in vivo standpoint, the objective of this study was to utilize flow cytometry to prospectively determine monocyte Fcgamma (FcR) I, II, and III receptor expression levels in patients with acute coronary syndrome (ACS, n = 48), diabetes mellitus (DM, n = 59), or neither (C, n = 88). RESULTS: Increased FcR I expression was found in the ACS versus DM groups [geometric mean, (95% CI) = 2.26 (2.07, 2.47) versus 1.83 (1.69, 1.98) (p < 0.001)] and versus C [1.90 (1.78, 2.03) (p = 0.005)]. Similar relationships were found with both the FcR II receptor [ACS mean = 4.57 (4.02, 5.19) versus DM 3.61 (3.22, 4.05) (p = 0.021) and versus C 3.86 (3.51, 4.24) (p = 0.09)] and FcR III receptor [ACS mean = 1.55 (1.44, 1.68) versus DM 1.36 (1.27, 1.46) (p = 0.038) and versus C 1.37 (1.30, 1.45) (p = 0.032)]. There was no difference between DM and C groups in FcR I, II or III expression. CONCLUSIONS: This in vivo data supports a possible second OxLDL-autoantibody macrophage uptake mechanism through an Fc receptor-mediated pathway and a potential relationship between atherosclerotic plaque macrophage FcR levels and ACS.
authors.affiliation: Department of Medicine, University of Colorado, Denver, CO; USA. david.calverley@uchsc.edu.
authors.forename: David C
authors.initials: DC
authors.lastname: Calverley
authors.forename: Taya
authors.initials: T
authors.lastname: Varteresian
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Brass
authors.forename: Denice D
authors.initials: DD
authors.lastname: Tsao-Wei
authors.forename: Susan
authors.initials: S
authors.lastname: Groshen
authors.forename: Wendy J
authors.initials: WJ
authors.lastname: Mack
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Buchanan
authors.forename: Howard N
authors.initials: HN
authors.lastname: Hodis
authors.forename: Alan D
authors.initials: AD
authors.lastname: Schreiber