Atherosclerosis 176 (2004) 21–26 EGF mediates monocyte chemotaxis and macrophage proliferation and EGF receptor is expressed in atherosclerotic plaques David J. Lamb a,∗ , Helmout Modjtahedi b , Nicholas J. Plant c , Gordon A.A. Ferns a,d a Centre for Clinical Science & Measurement, School of Biomedical & Molecular Sciences, University of Surrey, Guildford, Surrey, GU2 7XH, UK b Centre for Clinical Science & Measurement, Postgraduate Medical School, University of Surrey, Guildford, Surrey, GU2 7XH, UK c Molecular Toxicology, School of Biomedical & Molecular Sciences, University of Surrey, Guildford, Surrey, GU2 7XH, UK d Clinical Laboratory, Royal Surrey County Hospital, Guildford, Surrey, GU2 5XX, UK Received 29 August 2003; received in revised form 19 February 2004; accepted 20 April 2004 Available online 24 June 2004 Abstract The recruitment of peripheral monocytes to the sub-endothelial space, their development into macrophages and subsequent proliferation are critical events during atherosclerosis. Receptors for epidermal growth factor (EGF) have been identified on cells of the myeloid lineage, but a role for them in atherogenesis has yet to be described. We have identified functional EGF receptors (EGFR, ErbB1/HER-1) on peripheral blood monocytes and monocyte-derived macrophages. Uniquely, these receptors were found to mediate both chemotaxis in monocytes and macrophages and proliferation in macrophages. EGFR mRNA was detected in atherosclerotic plaques, but not in morphologically normal aortae and EGFR receptor staining co-localised with macrophage staining in these plaques. The identification of receptors for EGF on peripheral blood monocytes, macrophages and atherosclerotic lesions, together with their transduction of two functionally important cellular events, heightens the potential importance of members of the EGF super-family in atherogenesis and other chronic inflammatory processes. © 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: EGF; Macrophage; Atherosclerotic plaques 1. Introduction The human epidermal growth factor (EGF) receptor (EGFR, HER-1, ErbB1) is a 170 kDa transmembrane recep- tor tyrosine kinase [1]. Three other homologous members of the EGF receptor gene family have been described; ErbB2, ErbB3 and ErbB4 [1]. The functional EGF receptor consists of dimeric combinations of these subunits. EGFR ligands include EGF, heparin binding EGF (HB-EGF), transforming growth factor- (TGF-), amphiregulin (AR), betacellulin (BTC) and epiregulin (ER) [1]. The other members of the EGF receptor family have differential binding specificities to members of the EGF superfamily [1]. We have produced and characterised a series of rat monoclonal antibodies that specifically recognize the external domain of EGFR/HER-1 [2]. ∗ Corresponding author. Tel.: +44 1483 682599; fax: +44 1483 876481. E-mail address: d.lamb@surrey.ac.uk (D.J. Lamb). There have been previous reports that cells of the myeloid lineage, for example glial cells [3], tumour-associated macrophages [4], and the human monocytic cell line, U937 [5], express EGFR, but a functional role has not been identified. The aim of this study was to determine whether the EGF receptor, EGFR, is expressed on peripheral mono- cytes and/or macrophages, whether or not it mediates cell function and whether there is a potential role for EGFR in atherogenesis. 2. Methods 2.1. Reagents All reagents were purchased from Sigma (Poole, Dorset, UK) unless otherwise stated. 2.2. Mononuclear cell & macrophage isolation Mononuclear cells were isolated from whole blood by density centrifugation using Histopaque 1083 (r) (Sigma, 0021-9150/$ – see front matter © 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.atherosclerosis.2004.04.012