Harvard Medical School, USA
Guo-Ping Shi received his doctoral training in Physiology from Harvard University in 1995. He is currently a Biochemist of Cardiovascular Medicine, Brigham and Women’s Hospital and an Associate Professor of Medicine, Harvard Medical School. His research team has longstanding interest in the roles of lysosomal cysteine proteases cathepsins and infl ammatory cells, mainly mast cells in the pathogenesis of atherosclerosis, abdominal aortic aneurysms, obesity, and diabetes. He has published more than 130 peer-reviewed articles in these fields, and serving as an editorial board member of 8 journals.
Mast cells (MCs) are pro-infl ammatory cells participating importantly in diet-induced obesity and diabetes. Th ese cells release pro-infl ammatory interleukin-6 (IL6) and interferon- (IFN-) to induce vascular cell proteases expression and promote adipose tissue neovascularization. Reduced body weight gain and improved diabetes in MC-defi cient KitW-sh-W-sh mice can be reversed by adoptive transfer of in vitro prepared MCs from wild-type (WT) mice but not those from IL6- or IFN--defi cient mice. We have recently demonstrated that MCs from leptin-defi cient ob/ob mice also failed to reverse reduced obesity and diabetes in KitW-sh-W-sh mice. White adipose tissue (WAT) from KitW-sh-W-sh mice receiving MCs from ob/ob mice had signifi cantly smaller adipocyte size, fewer infl ammatory cell infi ltrates, lower pro-infl ammatory M1 macrophages, and higher anti-infl ammatory M2 macrophages than did WAT from KitW-sh-W-sh mice receiving WT MCs. In cultured mouse bone marrow-derived macrophages (BMDMs), co-culture of MCs from ob/ob mice protected BMDMs from lipopolysaccharide (LPS)-induced M1 macrophage diff erentiation and enhanced CD4+ T-cell-induced M2 macrophage diff erentiation. In contrast, leptin defi ciency did not aff ect CD4+ T-cell and CD8+ T-cell activities in regulating LPS- or CD4+ T-cell-induced M1 and M2 macrophage diff erentiations. MCs from ob/ob mice produced more anti-infl ammatory cytokines IL4 and IL13 and less pro-infl ammatory cytokine IL6 than did MCs from WT mice. Th ese observations suggest an anti-infl ammatory activity of MCs in the absence of leptin. When ob/ob mice became obese and diabetic, MC-defi cient KitW-sh-W-sh ob/ob mice gained even more body weight and developed more severe glucose tolerance. Th erefore, functional expression of leptin from MCs determines MC infl ammatory activities and experimental obesity and diabetes.