TY - JOUR
T1 - Neutrophil secretion products pave the way for inflammatory monocytes
AU - Soehnlein, Oliver
AU - Zernecke, Alma
AU - Eriksson, Einar E.
AU - Rothfuchs, Antonio Gigliotti
AU - Pham, Christine T.
AU - Herwald, Heiko
AU - Bidzhekov, Kiril
AU - Rottenberg, Martin E.
AU - Weber, Christian
AU - Lindbom, Lennart
PY - 2008
Y1 - 2008
N2 - 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 cremasterand 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 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.
AB - 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 cremasterand 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 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.
U2 - 10.1182/blood-2008-02-139634
DO - 10.1182/blood-2008-02-139634
M3 - Article
C2 - 18490516
SN - 1528-0020
VL - 112
SP - 1461
EP - 1471
JO - Blood
JF - Blood
IS - 4
ER -