EGF mediates monocyte chemotaxis and macrophage proliferation and EGF receptor is expressed in atherosclerotic plaques.
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.
Lamb
David J
DJ
Centre for Clinical Science & Measurement, School of Biomedical & Molecular Sciences, University of Surrey, Guildford, Surrey, GU2 7XH, UK. d.lamb@surrey.ac.uk
Modjtahedi
Helmout
H
Plant
Nicholas J
NJ
Ferns
Gordon A A
GA
D000818:Animals; D001011:Aorta / Q000276:immunology / Q000503:physiopathology; D001161:Arteriosclerosis / Q000276:immunology* / Q000503:physiopathology; D002455:Cell Division / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology*; D004815:Epidermal Growth Factor / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression / Q000276:immunology; D008264:Macrophages / Q000166:cytology* / Q000502:physiology; D008934:Mitogens / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology* / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits
D008934:Mitogens; D012333:RNA, Messenger; D004815:Epidermal Growth Factor; D066246:ErbB Receptors