Functional Analysis of Monocyte Subsets in Surgical Sepsis

Schinkel, Christian; Sendtner, Raimund; Zimmer, S; Faist, E.

doi:10.1097/00005373-199707000-00112

Cited by 28 publications

(45 citation statements)

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“…A recent comparison between human and mouse monocytes indicated that CX 3 CR1 low (our Ly-6C high ) monocytes correspond to the classical CD14 high CD16 Ϫ monocytes, whereas CX 3 CR1 high (our Ly-6C Ϫ/low ) monocytes resemble CD14 low CD16 high cells (14). Interestingly, in human patients with sepsis an increase has been observed of CD64 ϩ monocytes, which primarily correspond to the major subset of CD14 ϩ 16 Ϫ monocytes (31). In analogy to our findings in infected mice, this might represent a so-called left shift toward immature monocytes also in severe inflammations in humans.…”

Section: Discussionmentioning

confidence: 59%

Subpopulations of Mouse Blood Monocytes Differ in Maturation Stage and Inflammatory Response

Sunderkötter

Nikolić

Dillon

et al. 2004

The Journal of Immunology

990

1,097

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Blood monocytes are well-characterized precursors for macrophages and dendritic cells. Subsets of human monocytes with differential representation in various disease states are well known. In contrast, mouse monocyte subsets have been characterized minimally. In this study we identify three subpopulations of mouse monocytes that can be distinguished by differential expression of Ly-6C, CD43, CD11c, MBR, and CD62L. The subsets share the characteristics of extensive phagocytosis, similar expression of M-CSF receptor (CD115), and development into macrophages upon M-CSF stimulation. By eliminating blood monocytes with dichloromethylene-bisphosphonate-loaded liposomes and monitoring their repopulation, we showed a developmental relationship between the subsets. Monocytes were maximally depleted 18 h after liposome application and subsequently reappeared in the circulation. These cells were exclusively of the Ly-6Chigh subset, resembling bone marrow monocytes. Serial flow cytometric analyses of newly released Ly-6Chigh monocytes showed that Ly-6C expression on these cells was down-regulated while in circulation. Under inflammatory conditions elicited either by acute infection with Listeria monocytogenes or chronic infection with Leishmania major, there was a significant increase in immature Ly-6Chigh monocytes, resembling the inflammatory left shift of granulocytes. In addition, acute peritoneal inflammation recruited preferentially Ly-6Cmed-high monocytes. Taken together, these data identify distinct subpopulations of mouse blood monocytes that differ in maturation stage and capacity to become recruited to inflammatory sites.

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Section: Discussionmentioning

confidence: 59%

Subpopulations of Mouse Blood Monocytes Differ in Maturation Stage and Inflammatory Response

Sunderkötter

Nikolić

Dillon

et al. 2004

The Journal of Immunology

990

1,097

View full text Add to dashboard Cite

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“…38 Classical human monocytes are potent phagocytes 39 and produce higher amounts of cytokines like IL-6 and TNF. 40,41 In contrast, nonclassical monocytes are potent antigen-presenting cells. 42 Such distinct differences have not yet been described for the murine equivalent.…”

Section: Discussionmentioning

confidence: 99%

Neutrophil secretion products pave the way for inflammatory monocytes

Soehnlein

Zernecke

Eriksson

et al. 2008

Blood

368

341

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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/...

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“…This population of murine monocytes shares morphological characteristics and chemokine receptor expression patterns with the classical human CD14 hi CD16 -monocytes, and murine resident monocytes are thought to correspond to human CD14 ϩ CD16 ϩ nonclassical monocytes [34]. Human classical monocytes are potent phagocytes [37] and produce higher amounts of cytokines such as IL-6 and TNF-␣ [38,39]. In contrast, nonclassical monocytes are potent APC [40].…”

Section: Azurocidin Induces Recruitment Of Monocytesmentioning

confidence: 99%

Neutrophil-derived azurocidin alarms the immune system

Soehnlein

Lindbom

2008

Journal of Leukocyte Biology

102

100

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Azurocidin (heparin-binding protein/ cationic antimicrobial protein of 37 kD) is a protein that is mobilized rapidly from emigrating polymorphonuclear leukocytes (PMN). Initially, this inactive serine protease was recognized for its antimicrobial effects. However, it soon became apparent that azurocidin may act to alarm the immune system in different ways and thus serve as an important mediator during the initiation of the immune response. Azurocidin, released from PMN secretory vesicles or primary granules, acts as a chemoattractant and activator of monocyte and macrophages. The functional consequence is enhancement of cytokine release and bacterial phagocytosis, allowing for a more efficient bacterial clearance. Leukocyte activation by azurocidin is mediated via ␤ 2 -integrins, and azurocidin-induced chemotaxis is dependent on formyl-peptide receptors. In addition, azurocidin activates endothelial cells leading to vascular leakage and edema formation. For these reasons, targeting azurocidin release and its actions may have therapeutic potential in inflammatory disease conditions. J. Leukoc. Biol. 85: 344 -351; 2009.

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Functional Analysis of Monocyte Subsets in Surgical Sepsis

Cited by 28 publications

References 0 publications

Subpopulations of Mouse Blood Monocytes Differ in Maturation Stage and Inflammatory Response

Subpopulations of Mouse Blood Monocytes Differ in Maturation Stage and Inflammatory Response

Neutrophil secretion products pave the way for inflammatory monocytes

Neutrophil-derived azurocidin alarms the immune system

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