PMID- 18208975 OWN - NLM STAT- MEDLINE DCOM- 20080317 LR - 20211020 IS - 1540-9538 (Electronic) IS - 0022-1007 (Print) IS - 0022-1007 (Linking) VI - 205 IP - 2 DP - 2008 Feb 18 TI - iPLA2beta: front and center in human monocyte chemotaxis to MCP-1. PG - 347-59 LID - 10.1084/jem.20071243 [doi] AB - Monocyte chemoattractant protein-1 (MCP-1) directs migration of blood monocytes to inflamed tissues. Despite the central role of chemotaxis in immune responses, the regulation of chemotaxis by signal transduction pathways and their in vivo significance remain to be thoroughly deciphered. In this study, we examined the intracellular location and functions of two recently identified regulators of chemotaxis, Ca(2+)-independent phospholipase (iPLA(2)beta) and cytosolic phospholipase (cPLA(2)alpha), and substantiate their in vivo importance. These enzymes are cytoplasmic in unstimulated monocytes. Upon MCP-1 stimulation, iPLA(2)beta is recruited to the membrane-enriched pseudopod. In contrast, cPLA(2)alpha is recruited to the endoplasmic reticulum. Although iPLA(2)beta or cPLA(2)alpha antisense oligodeoxyribonucleotide (ODN)-treated monocytes display reduced speed, iPLA(2)beta also regulates directionality and actin polymerization. iPLA(2)beta or cPLA(2)alpha antisense ODN-treated adoptively transferred mouse monocytes display a profound defect in migration to the peritoneum in vivo. These converging observations reveal that iPLA(2)beta and cPLA(2)alpha regulate monocyte migration from different intracellular locations, with iPLA(2)beta acting as a critical regulator of the cellular compass, and identify them as potential targets for antiinflammatory strategies. FAU - Mishra, Ravi S AU - Mishra RS AD - Department of Cell Biology, Cleveland Clinic, Cleveland, OH 44195, USA. FAU - Carnevale, Kevin A AU - Carnevale KA FAU - Cathcart, Martha K AU - Cathcart MK LA - eng GR - M01-RR-018390/RR/NCRR NIH HHS/United States GR - M01 RR018390/RR/NCRR NIH HHS/United States GR - HL 61971/HL/NHLBI NIH HHS/United States GR - R01 HL061971/HL/NHLBI NIH HHS/United States GR - HL 510681/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20080121 PL - United States TA - J Exp Med JT - The Journal of experimental medicine JID - 2985109R RN - 0 (Actins) RN - 0 (Arachidonic Acids) RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Naphthalenes) RN - 0 (Oligodeoxyribonucleotides, Antisense) RN - 0 (Pyrones) RN - 00XIW1CR0F (arachidonyltrifluoromethane) RN - 88070-98-8 (6-(bromomethylene)tetrahydro-3-(1-naphthaleneyl)-2H-pyran-2-one) RN - EC 3.1.1.4 (Group IV Phospholipases A2) RN - EC 3.1.1.4 (Group VI Phospholipases A2) RN - EC 3.1.1.4 (PLA2G6 protein, human) SB - IM MH - Actins/metabolism MH - Adoptive Transfer MH - Animals MH - Arachidonic Acids/pharmacology MH - Cells, Cultured MH - Chemokine CCL2/*immunology MH - Chemotaxis/drug effects/immunology MH - Female MH - Group IV Phospholipases A2/antagonists & inhibitors/*immunology MH - Group VI Phospholipases A2/antagonists & inhibitors/*immunology MH - Humans MH - Leukocytes, Mononuclear/immunology MH - Mice MH - Mice, Inbred BALB C MH - Monocytes/drug effects/*immunology MH - Naphthalenes/pharmacology MH - Oligodeoxyribonucleotides, Antisense/pharmacology MH - Peritonitis/chemically induced/immunology MH - Pyrones/pharmacology PMC - PMC2271028 EDAT- 2008/01/23 09:00 MHDA- 2008/03/18 09:00 PMCR- 2008/08/18 CRDT- 2008/01/23 09:00 PHST- 2008/01/23 09:00 [pubmed] PHST- 2008/03/18 09:00 [medline] PHST- 2008/01/23 09:00 [entrez] PHST- 2008/08/18 00:00 [pmc-release] AID - jem.20071243 [pii] AID - 20071243 [pii] AID - 10.1084/jem.20071243 [doi] PST - ppublish SO - J Exp Med. 2008 Feb 18;205(2):347-59. doi: 10.1084/jem.20071243. Epub 2008 Jan 21.