title: Neutrophil-derived cathelicidin promotes adhesion of classical monocytes.
abstract: BACKGROUND
  The leukocyte response in acute inflammation is characterized by an initial recruitment of neutrophils preceding a second wave of monocytes. Neutrophil-derived granule proteins were suggested to hold an important role in this cellular switch. The exact mechanisms by which neutrophils mediate these processes are only partially understood.
  
  
  OBJECTIVE
  To investigate the role of neutrophils and their granule contents in the adhesion of monocyte subpopulations in acute inflammation.
  
  
  RESULTS
  Here, we show that neutrophil-derived cathelicidins (human: LL37, mouse: CRAMP) induce adhesion of classical monocytes but not of nonclassical monocytes in the mouse cremaster muscle and in in vitro flow chamber assays. CRAMP is released from emigrated neutrophils and then transported across the endothelium, where it is presented to rolling leukocytes. Endothelial-bound cathelicidin activates formyl-peptide receptor 2 on classical monocytes, resulting in monocytic β1- and β2-integrin conformational change toward an extended, active conformation that allows for adhesion to their respective ligands, vascular cell adhesion molecule 1 and intercellular adhesion molecule 1.
  
  
  CONCLUSIONS
  These data elucidate a novel mechanism of neutrophil-mediated monocyte recruitment, which could be targeted in conditions where recruitment of classical monocytes plays an unfavorable role.
authors.affiliation: Institute for Cardiovascular Prevention, LMU Munich, Pettenkoferstrasse 9, Munich, Germany.
authors.forename: Sarawuth
authors.initials: S
authors.lastname: Wantha
authors.forename: Jean-Eric
authors.initials: JE
authors.lastname: Alard
authors.forename: Remco T A
authors.initials: RT
authors.lastname: Megens
authors.forename: Anne M
authors.initials: AM
authors.lastname: van der Does
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Döring
authors.forename: Maik
authors.initials: M
authors.lastname: Drechsler
authors.forename: Christine T N
authors.initials: CT
authors.lastname: Pham
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Wang
authors.forename: Ji-Min
authors.initials: JM
authors.lastname: Wang
authors.forename: Richard L
authors.initials: RL
authors.lastname: Gallo
authors.forename: Philipp
authors.initials: P
authors.lastname: von Hundelshausen
authors.forename: Lennart
authors.initials: L
authors.lastname: Lindbom
authors.forename: Tilman
authors.initials: T
authors.lastname: Hackeng
authors.forename: Christian
authors.initials: C
authors.lastname: Weber
authors.forename: Oliver
authors.initials: O
authors.lastname: Soehnlein
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism*; D054804:Cathelicidins / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication / Q000502:physiology*; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D016023:Integrins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology*; D009504:Neutrophils / Q000378:metabolism* / Q000473:pathology*; D044042:Receptors, Formyl Peptide / Q000378:metabolism; D044067:Receptors, Lipoxin / Q000378:metabolism
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; C105101:FPR2 protein, human; D016023:Integrins; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; C481578:formyl peptide receptor 2, mouse