Association between monocyte Fcγ subclass expression and acute coronary syndrome

David Calverley, Taya Varteresian, Elizabeth Brass, Denice D. Tsao-Wei, Susan Groshen, Wendy J. Mack, Thomas A. Buchanan, Howard N. Hodis, Alan D. Schreiber

Research output: Contribution to journalArticle

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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 Fcγ (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.

Original languageEnglish (US)
Article number4
JournalImmunity and Ageing
Volume1
DOIs
StatePublished - Nov 12 2004
Externally publishedYes

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Acute Coronary Syndrome
Monocytes
Fc Receptors
Macrophages
Autoantibodies
Scavenger Receptors
Foam Cells
Atherosclerotic Plaques
Endocytosis
Immunoglobulins
Atherosclerosis
Diabetes Mellitus
Flow Cytometry
Immunoglobulin G
oxidized low density lipoprotein

ASJC Scopus subject areas

  • Immunology
  • Aging

Cite this

Calverley, D., Varteresian, T., Brass, E., Tsao-Wei, D. D., Groshen, S., Mack, W. J., ... Schreiber, A. D. (2004). Association between monocyte Fcγ subclass expression and acute coronary syndrome. Immunity and Ageing, 1, [4]. https://doi.org/10.1186/1742-4933-1-4

Association between monocyte Fcγ subclass expression and acute coronary syndrome. / Calverley, David; Varteresian, Taya; Brass, Elizabeth; Tsao-Wei, Denice D.; Groshen, Susan; Mack, Wendy J.; Buchanan, Thomas A.; Hodis, Howard N.; Schreiber, Alan D.

In: Immunity and Ageing, Vol. 1, 4, 12.11.2004.

Research output: Contribution to journalArticle

Calverley, D, Varteresian, T, Brass, E, Tsao-Wei, DD, Groshen, S, Mack, WJ, Buchanan, TA, Hodis, HN & Schreiber, AD 2004, 'Association between monocyte Fcγ subclass expression and acute coronary syndrome', Immunity and Ageing, vol. 1, 4. https://doi.org/10.1186/1742-4933-1-4
Calverley D, Varteresian T, Brass E, Tsao-Wei DD, Groshen S, Mack WJ et al. Association between monocyte Fcγ subclass expression and acute coronary syndrome. Immunity and Ageing. 2004 Nov 12;1. 4. https://doi.org/10.1186/1742-4933-1-4
Calverley, David ; Varteresian, Taya ; Brass, Elizabeth ; Tsao-Wei, Denice D. ; Groshen, Susan ; Mack, Wendy J. ; Buchanan, Thomas A. ; Hodis, Howard N. ; Schreiber, Alan D. / Association between monocyte Fcγ subclass expression and acute coronary syndrome. In: Immunity and Ageing. 2004 ; Vol. 1.
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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 Fcγ (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.",
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AU - Calverley, David

AU - Varteresian, Taya

AU - Brass, Elizabeth

AU - Tsao-Wei, Denice D.

AU - Groshen, Susan

AU - Mack, Wendy J.

AU - Buchanan, Thomas A.

AU - Hodis, Howard N.

AU - Schreiber, Alan D.

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N2 - 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 Fcγ (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.

AB - 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 Fcγ (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.

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