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 PMNdepleting antibody, the extravasation of inflammatory monocytes, but not resident monocytes, was markedly reduced compared with mice with intact white blood cell IntroductionPolymorphonuclear leukocytes (PMN) dominate the initial leukocyte influx to sites of acute infection and inflammation. 1 This first wave of PMN extravasation precedes a second wave of monocyte extravasation. Recruited PMN are thought to trigger this cellular switch by releasing soluble factors that initiate monocyte recruitment, 2-4 much of which may be mediated by ready-made PMN granule proteins deposited at the site of inflammation. 5,6 Indeed, supernatants of activated PMN from patients with specific granule deficiency lacking proteins in their primary, secondary, and tertiary granules show a reduced capacity to attract monocytes despite normal monocyte chemotaxis in vitro to other stimuli. 7 After this initial observation, several PMN-derived granule proteins with monocyte-chemotactic activity were identified, among them LL-37, cathepsin G, human neutrophil peptide 1-3 (HNP1-3, ␣-defensins), and heparin-binding protein (HBP, also known as CAP37 and azurocidin). [8][9][10][11] Their action was found to be pertussis toxin (PTx)-sensitive and several receptors were suggested to mediate the chemotactic effect. [11][12][13] Peripheral blood monocytes constitute a heterogeneous population of circulating leukocytes in both humans 14 and mice. 15 In the murine blood, 2 monocyte subsets can be distinguished based on their expression of CX3CR1, CCR2, and Gr1. Whereas resident monocytes (Gr1 Ϫ CCR2 Ϫ CX3CR1 hi ) home to noninflamed tissues, inflammatory monocytes (Gr1 ϩ CCR2 ϩ CX3CR1 lo ) are predominantly recruited to sites of inflammation by mechanisms involving CCR2. 15 These inflammatory monocytes were recently shown to be of critical importance in diverse inflammatory and infectious diseases. [16][17][18][19] In this study, we investigated the significance of the initial PMN efflux for the subsequent extravasation of monocytes. Our results demonstrate that PMN seed granule proteins in the tissue which contribute to mobilization specifically of inflammatory monocytes. Functionally, the PMN-dependent invasion of inflammatory monocytes results in a more vigorous immune response as shown by enhanced cytokine release and bacterial clearance at the site of inflammation. Methods AnimalsWild-type C57BL/...

Neutrophil-derived azurocidin alarms the immune system

“…A member of the formyl peptide receptor (FPR) family has been identified recently as the receptor for cathepsin G on leukocytes mediating its chemotactic effect [59]. In line with this, it was demonstrated recently that FPR antagonists efficiently block the chemotactic response of inflammatory monocytes to azurocidin in vivo, suggesting that a member of this family is important in mediating azurocidin-dependent chemotaxis [35].…”

“…It was demonstrated recently that azurocidin specifically stimulates efflux of inflammatory monocytes (Fig. 1C) [35]. Murine inflammatory monocytes were defined as CX3CR1 lo CCR2 ϩ GR1 ϩ [36].…”

Egyptian Propolis 12: Influence of Propolis on Cytokines of Toxoplasma gondii Infected Rats

“…Masek and Hunter (2013) stated that macrophages can be infected by T. gondii, they are able to limit parasite replication and produce cytokines that contribute to resistance, making them important regulatory and effector cells during toxoplasmosis. Neutrophils influence the T-cell response by enhancing the functions of dendritic cells (van Gisbergen et al, 2005) or inflammatory monocytes (Soehnlein et al, 2008). Infection of mice by intraperitoneal (i.p.)…”

Antiinflammatory actions of inorganic nitrate stabilize the atherosclerotic plaque

“…In the early stages of atherosclerosis the neutrophil plays a key role, through the release of specific chemoattractant mediators, in the consequent recruitment of inflammatory monocytes to the athero-prone site (44,63). Using an acute model of inflammation, we have shown that treatment of ApoE KO mice with inorganic nitrate reduces first neutrophil recruitment, followed by consequent reductions in the number of inflammatory monocytes.…”