PMID- 12165536 OWN - NLM STAT- MEDLINE DCOM- 20020903 LR - 20220129 IS - 0022-1767 (Print) IS - 1550-6606 (Electronic) IS - 0022-1767 (Linking) VI - 169 IP - 4 DP - 2002 Aug 15 TI - Annexin 1 modulates monocyte-endothelial cell interaction in vitro and cell migration in vivo in the human SCID mouse transplantation model. PG - 2085-92 AB - The effect of the glucocorticoid inducible protein annexin 1 (ANXA1) on the process of monocytic cell migration was studied using transfected U937 cells expressing variable protein levels. An antisense (AS) (36.4AS; approximately 50% less ANXA1) and a sense (S) clone (15S; overexpressing the bioactive 24-kDa fragment) together with the empty plasmid CMV clone were obtained and compared with wild-type U937 cells in various models of cell migration in vitro and in vivo. 15S-transfected U937 cells displayed a reduced (50%) degree of trans-endothelial migration in response to stromal cell-derived factor-1alpha (CXC chemokine ligand 12 (CXCL12)). In addition, the inhibitory role of endogenous ANXA1 on U937 cell migration in vitro was confirmed by the potentiating effect of a neutralizing anti-ANXA1 serum. Importantly, overexpression of ANXA1 in clone 15S inhibited the extent of cell migration into rheumatoid synovial grafts transplanted into SCID mice. ANXA1 inhibitory effects were not due to modifications in adhesion molecule or CXCL12 receptor (CXCR4) expression as shown by the similar amounts of surface molecules found in transfected and wild-type U937 cells. Likewise, an equal chemotactic response to CXCL12 in vitro excluded an intrinsic defect in cell motility in clones 15S and 36.4AS. These data strongly support the notion that ANXA1 critically interferes with a leukocyte endothelial step essential for U937 cell, and possibly monocyte, transmigration both in vitro and in vivo. FAU - Perretti, Mauro AU - Perretti M AD - William Harvey Research Institute, London, United Kingdom. M.Perretti@qmul.ac.uk FAU - Ingegnoli, Francesca AU - Ingegnoli F FAU - Wheller, Samantha K AU - Wheller SK FAU - Blades, Mark C AU - Blades MC FAU - Solito, Egle AU - Solito E FAU - Pitzalis, Costantino AU - Pitzalis C LA - eng GR - WT_/Wellcome Trust/United Kingdom GR - 15718/ARC_/Arthritis Research UK/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Annexin A1) RN - 0 (CXCL12 protein, human) RN - 0 (Chemokine CXCL12) RN - 0 (Chemokines, CXC) RN - 0 (Cxcl12 protein, mouse) SB - IM MH - Amino Acid Sequence MH - Animals MH - Annexin A1/antagonists & inhibitors/genetics/*physiology MH - Cell Movement/physiology MH - Chemokine CXCL12 MH - Chemokines, CXC/pharmacology MH - Chemotaxis MH - Endothelium, Vascular/cytology/drug effects/*physiology MH - Gene Expression MH - Humans MH - In Vitro Techniques MH - Mice MH - Mice, SCID MH - Molecular Sequence Data MH - Monocytes/drug effects/*physiology MH - Synovial Membrane/transplantation MH - Transfection MH - Transplantation, Heterologous MH - U937 Cells PMC - PMC4340507 MID - EMS28034 OID - NLM: EMS28034 EDAT- 2002/08/08 10:00 MHDA- 2002/09/11 10:01 PMCR- 2015/02/25 CRDT- 2002/08/08 10:00 PHST- 2002/08/08 10:00 [pubmed] PHST- 2002/09/11 10:01 [medline] PHST- 2002/08/08 10:00 [entrez] PHST- 2015/02/25 00:00 [pmc-release] AID - 10.4049/jimmunol.169.4.2085 [doi] PST - ppublish SO - J Immunol. 2002 Aug 15;169(4):2085-92. doi: 10.4049/jimmunol.169.4.2085.