Neutrophil secretion products pave the way for inflammatory monocytes

Oliver Soehnlein, Alma Zernecke, Einar E. Eriksson, Antonio Gigliotti Rothfuchs, Christine T. Pham, Heiko Herwald, Kiril Bidzhekov, Martin E. Rottenberg, Christian Weber, Lennart Lindbom

Research output: Contribution to journalArticlepeer-review

288 Scopus citations

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-CCR2CX3CR1hl resident monocytes and Gr1+CCR2+CX3CR1Io 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 PAR 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.

Original languageEnglish
Pages (from-to)1461-1471
Number of pages11
JournalBlood
Volume112
Issue number4
DOIs
StatePublished - Aug 15 2008

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