Rabbit Anti-Human LAIR1 (internal) Polyclonal antibody

Conventional strategies are not particularly successful in the treatment of leukaemia, and identification of signalling pathways crucial to the activity of leukaemia stem cells will provide targets for the development of new therapies. Here we report that certain receptors containing the immunoreceptor tyrosine-based inhibition motif (ITIM) are crucial for the development of acute myeloid leukaemia (AML). Inhibition of expression of the ITIM-containing receptor LAIR1 does not affect normal haematopoiesis but abolishes leukaemia development. LAIR1 induces activation of SHP-1, which acts as a phosphatase-independent signalling adaptor to recruit CAMK1 for activation of downstream CREB in AML cells. The LAIR1-SHP-1-CAMK1-CREB pathway sustains the survival and self-renewal of AML stem cells. Intervention in the signalling initiated by ITIM-containing receptors such as LAIR1 may result in successful treatment of AML.

Purpose: A global gene expression microarray analysis of surplus chorionic villus sampling (CVS) tissues identified leukocyte-associated immunoglobulin-like receptor 2 (LAIR2) as down-regulated in the first trimester of pregnancies destined for preeclampsia. Neither the localization nor the function of LAIR2 has been examined in the placenta. Localization studies were conducted in placental tissues to determine the precise sites of LAIR2 mRNA production and protein binding. Results: Quantitative real time polymerase chain reaction (qRT-PCR) indicated LAIR2 expression in CVS, but none in breast, lymph node, kidney, skin, uterus, or third trimester placentas. In situ hybridization (ISH) revealed a highly restricted LAIR2 localization. LAIR2 mRNA was found only in the more distal portions of trophoblast anchoring cell columns, adjacent to the invading extravillous trophoblast (EVT). Immunohistochemistry (IHC) detected intracellular LAIR2 staining in these same cells. Extracellular staining of this soluble receptor was found in the acellular material between invasive EVT cells distal to the anchoring cell columns. Conclusions: ISH and IHC staining for LAIR2 detected specific, highly localized expression at the leading edge of EVT anchoring cell columns in first trimester placentas. This staining likely identifies the site of production for this soluble receptor. Following secretion, the receptor appears to bind extracellular material among the invasive EVT. The precise restriction of this protein only to the sites of EVT invasion strongly suggests that it functions to regulate this invasion. The decreased LAIR2 expression noted in first trimester placentas that ultimately developed preeclampsia further suggests that alterations in LAIR2 may play an etiologic role in preeclampsia. (C) 2010 Elsevier Ltd. All rights reserved.