title: Cyclophilin A cooperates with MIP-2 to augment neutrophil migration.
abstract: BACKGROUND
  Chemokines contribute to inflammatory responses by inducing leukocyte migration and extravasation. In addition, chemoattractants other than classical chemokines can also be present. Many chemokines have been demonstrated to cooperate, leading to an augmentation in leukocyte recruitment and providing a potential role for the presence of multiple chemoattractants. Extracellular cyclophilins are a group of alternative chemotactic factors, which can be highly elevated during various inflammatory responses and, as we have previously shown, can contribute significantly to neutrophil recruitment in an animal model of acute lung inflammation. In the current studies we investigated whether the most abundant extracellular cyclophilin, CypA, has the capacity to function in partnership with 2 classical chemokines known to be secreted in the same model, macrophage inflammatory protein (MIP)-2/CXCL2 and keratinocyte chemoattractant (KC)/CXCL1.
  
  
  METHODS
  Neutrophil migration in response to combinations of CypA and MIP-2 or CypA and KC was measured by in vitro chemotaxis assays. Biochemical responses of neutrophils incubated with the combinations of chemoattractants were determined by changes in chemokine receptor internalization and actin polymerization measured by flow cytometry, and changes in intracellular calcium mobilization measured with a calcium sensitive fluorochrome.
  
  
  RESULTS
  A combination of CypA and MIP-2, but not KC, augmented neutrophil migration. Based on the level of augmentation, the cooperation between CypA and MIP-2 appeared to be synergistic. Evidence that CypA and MIP-2 cooperate at the biochemical level was demonstrated by increases in receptor internalization, calcium mobilization, and actin polymerization.
  
  
  CONCLUSIONS
  These findings provide evidence for the capacity of extracellular cyclophilins to interact with classical chemokines, resulting in greater and more efficient leukocyte recruitment.
authors.affiliation: Department of Microbiology, Immunology and Tropical Medicine, The George Washington University, Washington, DC, USA.
authors.forename: Shannon J
authors.initials: SJ
authors.lastname: Heine
authors.forename: Denise
authors.initials: D
authors.lastname: Olive
authors.forename: Ji-Liang
authors.initials: JL
authors.lastname: Gao
authors.forename: Philip M
authors.initials: PM
authors.lastname: Murphy
authors.forename: Michael I
authors.initials: MI
authors.lastname: Bukrinsky
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Constant
references.citation: J Leukoc Biol. 2009 Sep;86(3):671-80
references.pmid: 19451399
references.citation: Mol Pharmacol. 2005 Feb;67(2):460-9
references.pmid: 15509716
references.citation: J Biol Chem. 2002 Jun 21;277(25):22959-65
references.pmid: 11943775
references.citation: Cell. 2002 Nov 27;111(5):635-46
references.pmid: 12464176
references.citation: Eur J Immunol. 2005 Mar;35(3):746-56
references.pmid: 15714581
references.citation: J Leukoc Biol. 2011 Mar;89(3):359-72
references.pmid: 21097697
references.citation: J Infect Dis. 1996 Jan;173(1):159-65
references.pmid: 8537653
references.citation: Eur J Immunol. 2009 Apr;39(4):1118-28
references.pmid: 19291700
references.citation: Glycobiology. 2007 May;17(5):492-503
references.pmid: 17267519
references.citation: Am J Respir Crit Care Med. 2002 Aug 1;166(3):268-73
references.pmid: 12153956
references.citation: Mol Pharmacol. 2002 Jul;62(1):173-80
references.pmid: 12065768
references.citation: Eur J Immunol. 2005 May;35(5):1583-91
references.pmid: 15827963
references.citation: Int J Cancer. 2011 May 1;128(9):1999-2009
references.pmid: 21387284
references.citation: Cell Immunol. 2004 Jul;230(1):23-32
references.pmid: 15541716
references.citation: EMBO J. 2001 May 15;20(10):2497-507
references.pmid: 11350939
references.citation: Biochem Biophys Res Commun. 2001 Nov 9;288(4):786-8
references.pmid: 11688976
references.citation: Cytokine Growth Factor Rev. 2005 Dec;16(6):561-80
references.pmid: 16023396
references.citation: J Immunol. 2005 Jul 1;175(1):517-22
references.pmid: 15972687
references.citation: Trends Immunol. 2002 Jul;23(7):323-5
references.pmid: 12103338
references.citation: J Leukoc Biol. 2004 Jul;76(1):185-94
references.pmid: 15075362
references.citation: Blood. 2001 Apr 15;97(8):2197-204
references.pmid: 11290579
references.citation: Mol Pharmacol. 2008 Aug;74(2):485-95
references.pmid: 18469140
references.citation: Immunology. 2009 Jan;126(1):55-62
references.pmid: 18557953
references.citation: J Immunol. 2006 Oct 1;177(7):4870-9
references.pmid: 16982929
references.citation: Immunology. 2006 Mar;117(3):301-9
references.pmid: 16476049
references.citation: J Exp Med. 1997 Mar 3;185(5):975-80
references.pmid: 9120404
references.citation: J Clin Immunol. 1997 Sep;17(5):380-6
references.pmid: 9327337
references.citation: Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3511-5
references.pmid: 1565646
references.citation: Toxicology. 1995 Dec 28;105(2-3):161-79
references.pmid: 8571354
references.citation: Biochem J. 1998 Dec 15;336 ( Pt 3):689-97
references.pmid: 9841882
references.citation: Arterioscler Thromb Vasc Biol. 2004 Jul;24(7):1186-91
references.pmid: 15130913
references.citation: Circ Res. 2000 Oct 27;87(9):789-96
references.pmid: 11055983
references.citation: EMBO J. 1999 Dec 1;18(23):6771-85
references.pmid: 10581250
references.citation: J Leukoc Biol. 2003 Nov;74(5):791-9
references.pmid: 12960247
references.citation: J Immunol. 1999 Sep 1;163(5):2829-35
references.pmid: 10453028
references.citation: Infect Immun. 2004 Dec;72(12):7247-56
references.pmid: 15557650