title: Neutrophil secretion products pave the way for inflammatory monocytes.
abstract: The leukocyte response in inflammation is characterized by an initial recruitment of polymorphonuclear leukocytes (PMN) preceding a second wave of monocytes to the site of injury or infection. In the mouse, 2 populations of monocytes have been identified, Gr1(-)CCR2(-)CX3CR1(hi) resident monocytes and Gr1(+)CCR2(+)CX3CR1(lo) inflammatory monocytes. Here, intravital microscopy of the musculus cremaster and a subcutaneous air pouch model were used to investigate a possible link between PMN extravasation and the subsequent emigration of inflammatory monocytes in response to local stimulation with PAF. In mice that were made neutropenic by injection of a PMN-depleting antibody, the extravasation of inflammatory monocytes, but not resident monocytes, was markedly reduced compared with mice with intact white blood cell count but was restored by local treatment with secretion of activated PMN. Components of the PMN secretion were found to directly activate inflammatory monocytes and further examination revealed PMN-derived LL-37 and heparin-binding protein (HBP/CAP37/azurocidin) as primary mediators of the recruitment of inflammatory monocytes via activation of formyl-peptide receptors. These data show that LL-37 and HBP specifically stimulate mobilization of inflammatory monocytes. This cellular cross-talk functionally results in enhanced cytokine levels and increased bacterial clearance, thus boosting the early immune response.
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden. oliver.sohnlein@ki.se
authors.forename: Oliver
authors.initials: O
authors.lastname: Soehnlein
authors.forename: Alma
authors.initials: A
authors.lastname: Zernecke
authors.forename: Einar E
authors.initials: EE
authors.lastname: Eriksson
authors.forename: Antonio Gigliotti
authors.initials: AG
authors.lastname: Rothfuchs
authors.forename: Christine T
authors.initials: CT
authors.lastname: Pham
authors.forename: Heiko
authors.initials: H
authors.lastname: Herwald
authors.forename: Kiril
authors.initials: K
authors.lastname: Bidzhekov
authors.forename: Martin E
authors.initials: ME
authors.lastname: Rottenberg
authors.forename: Christian
authors.initials: C
authors.lastname: Weber
authors.forename: Lennart
authors.initials: L
authors.lastname: Lindbom
mesh_terms: D000818:Animals; D000954:Antigens, Surface; D023181:Antimicrobial Cationic Peptides / Q000502:physiology*; D001424:Bacterial Infections / Q000276:immunology / Q000473:pathology; D054804:Cathelicidins; D056649:Cathepsin G; D002403:Cathepsins; D002634:Chemotaxis, Leukocyte; D007249:Inflammation / Q000276:immunology*; D051379:Mice; D009000:Monocytes / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D019899:Paracrine Communication / Q000276:immunology*; D010587:Phagocytosis; D054390:Receptors, CCR2; D012697:Serine Endopeptidases
chemical_list: D000954:Antigens, Surface; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; C515335:Ccr2 protein, mouse; D054390:Receptors, CCR2; D002403:Cathepsins; D012697:Serine Endopeptidases; D056649:Cathepsin G; C534096:Ctsg protein, mouse