Mechanisms of Leukocyte Recruitment

Group leader: Associate Professor Michael Hickey

The interest of our laboratory lies in understanding the mechanisms whereby leukocytes exit the bloodstream and enter sites of inflammation. Leukocyte recruitment underlies the pathology of inflammatory diseases such as asthma, arthritis, multiple sclerosis, psoriasis and diseases of the vasculature such as atherosclerosis, and as such is a major potential therapeutic target for these conditions.

To understand the molecular basis of this process, our laboratory uses various forms of advanced in vivo imaging, including multiphoton microscopy, to image tissues during the development of the inflammatory response. We have particular interests in inflammatory responses of the renal glomerulus and skin, and also examine the roles of proinflammatory cytokines such as macrophage migration inhibitory factor in regulation of this process.

Highlights of recent publications

FAN H, HALL P, SANTOS LL, GREGORY JL, FINGERLE-ROWSON G, BUCALA R, MORAND EF, HICKEY MJ. Macrophage migration inhibitory factor and CD74 regulate macrophage chemotactic responses via MAPK and Rho GTPase. J. Immunol (2011) 186: 4915-24.

DEVI S, KULIGOWSKI MP, KWAN RYQ, WESTEIN E, JACKSON SP, KITCHING AR, HICKEY MJ. Platelet recruitment to the inflamed glomerulus occurs via an a_IIbb₃ /GPVI dependent pathway. Am. J. Pathol. (2010) 177: 1131-1142.

CHENG Q, MCKEOWN SJ, SANTOS L, SANTIAGO FS, KHACHIGIAN LM, MORAND EF, HICKEY MJ. Macrophage migration inhibitory factor increases leukocyte-endothelial interactions in human endothelial cells via promotion of expression of adhesion molecules. J. Immunol. (2010) 185: 1238–1247.

KULIGOWSKI MP, KWAN RYQ, LO C, WONG C, JAMES WG, BOURGES D, OOI JD, ABEYNAIKE L, HALL P, KITCHING AR, HICKEY MJ. Anti-myeloperoxidase antibodies rapidly induce a4 integrin-dependent glomerular neutrophil adhesion. Blood (2009) 113: 6485-94.

NIE CQ, BERNARD NJ, NORMAN MU, AMANTE FH, LUNDIE RJ, CRABB BS, HEATH WR, ENGWERDA CR, HICKEY MJ, SCHOFIELD L, HANSEN DS. IP-10-mediated T cell homing promotes cerebral inflammation over splenic immunity to malaria infection. PLoS Pathogens, (2009) 5: e1000369. Epub 2009 Apr 3.

WOOLLARD KJ, SUHARTOYO A, HARRIS EE, EISENHARDT S, TOH A, JACKSON SP, PETER K, DART AM, HICKEY MJ, CHIN-DUSTING JPF. Pathophysiological levels of soluble P-selectin mediate adhesion of leukocytes to the endothelium through Mac-1 activation. Circ. Res. (2008) 103: 1128-38.

EYLES JL, HICKEY MJ, NORMAN MU, CROKER BA, ROBERTS AW, DRAKE SF, JAMES WG, METCALF D, CAMPBELL IK, WICKS IP. A key role for G-CSF-induced neutrophil production and trafficking during inflammatory arthritis. Blood (2008) 112: 5193-201.

WONG CHY, HERTZOG PJ, BOZINOVSKI S, HICKEY MJ*, CRACK PJ. Absence of glutathione peroxidase-1 (Gpx1) exacerbates cerebral ischemia-reperfusion injury by reducing post-ischemic microvascular perfusion. J. Neurochem (2008) 107: 241-252.

HICKEY MJ, KWAN RYQ, AWAD MM, KENNEDY CL, YOUNG LF, HALL P, CORDNER LM, LYRAS D, EMMINS JJ, ROOD JI. Molecular and cellular basis of microvascular perfusion deficits induced by Clostridium perfringens and Clostridium septicum. PLoS Pathogens (2008) 4 (4): e1000045. doi:10.1371.

BERNHAGEN J, KROHN R, LUE H, GREGORY JL, ZERNECKE A, KOENEN RR, DEWOR M, GEORGIEV I, SCHOBER A, LENG L, KOOISTRA T, FINGERLE-ROWSON G, GHEZZI P, KLEEMANN R, MCCOLL SR, BUCALA R, HICKEY MJ, WEBER C. MIF is a non-cognate ligand of CXC chemokine receptors in inflammatory and atherogenic cell recruitment. Nature Medicine (2007) 13: 587-596.