Sun Qi, Jin Hong-Jian, Bond Judith S
Pediatric Hematology/Oncology, Department of Pediatrics, Penn State University Children's Hospital, Hershey, Pa., USA.
Exp Hematol. 2009 Mar;37(3):346-56. doi: 10.1016/j.exphem.2008.10.016. Epub 2008 Dec 24.
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.
膜型金属蛋白酶与炎症性肠病有关，炎症性肠病涉及免疫细胞功能障碍。然而，膜型金属蛋白酶在免疫和血液系统中的作用仍未明确。在本报告中，我们证明膜型金属蛋白酶在血液系统中表达，膜型金属蛋白酶α/β基因敲除（α(-/-)/β(-/-)）小鼠血液中驻留单核细胞和自然杀伤（NK）细胞的患病率降低，同时骨髓中炎症单核细胞和NK细胞积聚。相比之下，T和B淋巴细胞不受膜型金属蛋白酶缺乏的影响。腹腔注射巯基乙酸诱导急性炎症后，膜型金属蛋白酶缺陷小鼠的体温高于野生型小鼠，这与炎症单核细胞的滞留有关，但血液中NK细胞的患病率持续较低。这些结果表明，膜型金属蛋白酶在单核细胞和NK细胞的稳态中起重要作用，可能参与这两种细胞从骨髓向外周的迁移和归巢。我们的发现是首次证明金属蛋白酶影响白细胞稳态的报告，这对理解血液系统的生理学和发病机制具有重要意义。
