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Publication : Disruption of the meprin alpha and beta genes in mice alters homeostasis of monocytes and natural killer cells.

First Author  Sun Q Year  2009
Journal  Exp Hematol Volume  37
Issue  3 Pages  346-56
PubMed ID  19110362 Mgi Jnum  J:146557
Mgi Id  MGI:3837907 Doi  10.1016/j.exphem.2008.10.016
Citation  Sun Q, et al. (2009) Disruption of the meprin alpha and beta genes in mice alters homeostasis of monocytes and natural killer cells. Exp Hematol 37(3):346-56
abstractText  Meprin metalloproteases are implicated in inflammatory bowel disease, which involves dysfunction of immune cells. However, the roles of meprins in the immune and hematological system remain uncharacterized. In this report, we demonstrate that meprins were expressed in the hematological system, and meprin alpha/beta null (alpha(-/-)/beta(-/-)) mice had decreased prevalence of resident monocytes and natural killer (NK) cells in blood, with a concomitant accumulation of inflammatory monocytes and NK cells in bone marrow. In contrast, T and B lymphocytes were not affected by meprin deficiency. In response to acute inflammation induced by intraperitoneal injection of thioglycollate, meprin-deficient mice exhibited higher body temperature than wild-type mice, which was correlated with retention of inflammatory monocytes, but persistent low prevalence of NK cells in blood. These results indicate that meprin metalloproteases play important roles in the homeostasis of monocytes and NK cells, and possibly are involved in egress of these two type cells from bone marrow and homing to the periphery. Our findings are the first report to demonstrate that metalloproteases affect homeostasis of leukocytes, which have important implications for understanding physiology of and pathogenesis in the hematological system.
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