he role of hepatocyte growth factor in the diferentiation of dendritic cells from peripheral blood monocytes Mehmet Sonmez, MD, Ercument Ovali, MD, Tamer Dikmen, MD, Mustafa Yilmaz, MD, Murat Erturk, MD, PhD, Bircan Sonmez, MD, Serdar B. Omay, MD, PhD. D endritic cells (DC) play an important role in the regulation of immune response and can be detected in all kind of tissues except brain, testis and eyes. 1,2 he morphology of these cells is not speciic of DCs and resembles many other cells like macrophages and B lymphocytes. herefore, not only morphological appearances but also functional characteristics await full description. 1,3 Dendritic cells can be cultured outside the body speciically for the applications of immunotherapy. During the diferentiation period, combinations of cytokines like granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-4 (IL- 4), tumor necrosis factor-α (TNF-α), stem cell factor (SCF), fms-like tyrosine kinase 3 ligand (Flt- 3L), interleukin-1β (IL-1β), interleukin-2 (IL-2), interleukin-6 (IL-6) and prostaglandin E2 (PGE2), are utilized. 4 After the inding of the receptor of hepatocyte growth factor (HGF), c-met in adults, it was hypothesized that HGF not only plays an important role in the hematopoiesis of fetal period, but also in adults. In the studies thereafter, the role of HGF in the proliferation and diferentiation of stem cells was demonstrated. 5,6 After the data showing HGF secretion from monocytes and monocyte precursors, it was found that HGF would play important roles in the monocyte and macrophage functions resulting in enhanced non-speciic immune responses. 7,8 It has also been reported that the efect of HGF on peripheral blood and cord blood monocytes may be so that HGF increases for instance the antigen presentation eiciency of monocytes in peripheral blood but not of the monocytes from cord blood. 9,10 However, it has been reported that HGF stimulates (diferentiates) the CD34+ cells into DCs and exerts even stronger stimulating efect than GM-CSF. 11 In another study, it was demonstrated that HGF receptor c-met is present in mouse DCs and that HGF has a signiicant efect on the functions of DCs. 12 In this study, we planned to clarify the efect of HGF on the DC diferentiation from peripheral 688 ABSTRACT Objective: To ind out the efects of hepatocyte growth factor (HGF) in the development of dendritic cells (DC) from the peripheral monocytes. Methods: he study was carried out in Black Sea Technical University Hospital, Trabzon, Turkey between 2003-2004. Seven diferent cytokine combinations were employed to assess phenotypical and functional diferences of DCs from the peripheral monocytes in serum free culture media. Peripheral monocytes were incubated in media with cytokines for 5 days. he tumor necrosis factor-α (TNF-α) was added to the cell culture on day 5 and incubated for another 2 days. Surface and co-stimulating molecules on the cells were assessed by lowcytometry. he functional capacity of the DCs was evaluated on day 7 by puriied protein derivative loading and subsequent lymphoproliferation test using methyl tetrazolium staining. Results: On the 5th day of incubation DC development was observed in all cytokine groups, but cells were superior in cultures maintained in the presence of interleukin- 4 combinations with granulocyte-macrophage colony stimulating factor (GM-CSF) or with GM-CSF+HGF. Moreover, the expression of surface and co-stimulating molecules increased signiicantly after incubation with TNF-α. he efect of PPD loaded-DCs on proliferation of lymphocytes was more striking in HGF containing groups. Conclusion: It was concluded that HGF supplemented cultures exert some additive efects in relation to function of monocyte-derived DCs. But HGF alone does not seem to augment monocyte-derived DC proliferation and maturation signiicantly. Saudi Med J 2007; Vol. 28 (5): 688-695 From the Department of Hematology (Sonmez M., Ovali, Dikmen, Yilmaz, Omay), Department of Microbiology (Erturk), Department of Nuclear Medicine (Sonmez B.), Karadeniz Technical University, School of Medicine, Trabzon, Turkey. Received 24th September 2006. Accepted 30th December 2006. Address correspondence and reprint request to: Dr. Mehmet Sönmez, Department of Hematology, Karadeniz Technical University, School of Medicine, Trabzon 61080, Turkey. Tel. +90 (462) 3775367. Fax. +90 (462) 3280704. E-mail: mesonmez@yahoo.com