Involvement of MIP-2 and CXCR2 in neutrophil infiltration following injection of late apoptotic cells into the peritoneal cavity

Iyoda, Takuya; Kobayashi, Yoshiro

doi:10.1023/b:appt.0000031450.95188.e7

Cited by 20 publications

(24 citation statements)

References 36 publications

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“…The neutrophil infiltration into the thymus after x-irradiation was significantly reduced by either anti-MIP-2 or anti-CXCR2 Abs, as previously reported for neutrophil infiltration induced by injection of late apoptotic cells (11), suggesting that the neutrophil infiltration in both cases is mediated mainly by MIP-2. It should be noted that these Abs are specific to MIP-2 and CXCR2, respectively, and that anti-MIP-2 Abs do not bind to KC (11).…”

Section: Discussionsupporting

confidence: 85%

“…It should be noted that these Abs are specific to MIP-2 and CXCR2, respectively, and that anti-MIP-2 Abs do not bind to KC (11). In man, the neutrophil infiltration is strictly regulated by IL-8, and its receptors, CXCR1 and CXCR2 (34 -37).…”

Section: Discussionmentioning

confidence: 99%

“…Eight hundred micrograms of anti-MIP-2 polyclonal Abs (pAb), anti-CXCR2 pAb, and anti-GST pAb were injected through a tail vein just before x-irradiation or 9 h after x-irradiation. These Abs were obtained as described previously, and were found to be specific to MIP-2 and CXCR2, respectively (11). At the indicated times, mice were sacrificed and thymi were obtained.…”

Section: Whole-body X-irradiationmentioning

confidence: 99%

“…In addition, we reported that injection of late apoptotic cells into the mouse peritoneal cavity caused the production of MIP-2 and infiltration of neutrophils, and that the macrophages ingesting and/or binding to apoptotic cells, which were isolated with a cell sorter, produced a similar amount of MIP-2 as in the case of coculturing of peritoneal exudate cells (PEC) 3 with apoptotic cells (9,10). Moreover, we recently showed that anti-MIP-2 and anti-CXCR2 Abs significantly suppressed the neutrophil infiltration caused by injection of apoptotic cells into the peritoneal cavity, suggesting that the neutrophil infiltration is mainly caused by MIP-2 (11).…”

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confidence: 94%

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Neutrophils Accelerate Macrophage-Mediated Digestion of Apoptotic Cells In Vivo as Well as In Vitro

Iyoda

Nagata

Akashi³

et al. 2005

The Journal of Immunology

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It is generally believed that the clearance of apoptotic cells does not lead to inflammation. In contrast, we previously found that injection of apoptotic cells into the peritoneal cavity induced the expression of an inflammatory chemokine, MIP-2, and infiltration of neutrophils, and that anti-MIP-2 Abs suppressed the infiltration significantly. Because our previous study showed that whole-body x-irradiation caused neutrophil infiltration into the thymus along with T cell apoptosis, we examined the role of neutrophils in apoptotic cell clearance. Neutrophil infiltration reached a peak 12 h after irradiation with 1 Gy of x-rays. Immunohistological analysis revealed that apoptotic cells disappeared dramatically from 10.5 to 12 h after x-irradiation. As neutrophils moved from an inner area of the cortex to the periphery, apoptotic cells disappeared concomitantly. Either anti-MIP-2 or anti-CXCR2 Abs suppressed neutrophil infiltration significantly, and the suppression of neutrophil infiltration by anti-MIP-2 Abs delayed the disappearance of apoptotic cells. Moreover, macrophage-mediated digestion of apoptotic thymocytes was accelerated in vitro on coculturing with neutrophils, even if neutrophils were separated from macrophages. These results suggest that neutrophils are recruited to the thymus mainly by MIP-2 after whole-body x-irradiation and that such neutrophils may not induce inflammation but rather accelerate complete digestion of apoptotic cells by macrophages.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Whole-body X-irradiationmentioning

confidence: 99%

mentioning

confidence: 94%

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Neutrophils Accelerate Macrophage-Mediated Digestion of Apoptotic Cells In Vivo as Well as In Vitro

Iyoda

Nagata

Akashi³

et al. 2005

The Journal of Immunology

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“…We favor the latter explanation, because the presence of apoptotic neutrophils that are not rapidly cleared can lead to secondary necrosis and cell lysis, releasing proinflammatory mediators (16). In addition, although engulfment of apoptotic cells triggers antiinflammatory mediator release from macrophages, engulfment of late apoptotic or necrotic cells triggers proinflammatory mediator release (36). The mechanisms involved in both scenarios may have contributed to further neutrophil recruitment.…”

Section: Discussionmentioning

confidence: 99%

Transglutaminase 2 limits murine peritoneal acute gout‐like inflammation by regulating macrophage clearance of apoptotic neutrophils

Rose¹,

Sydlaske²,

Agha-Babakhani³

et al. 2006

Arthritis & Rheumatism

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Objective. Monosodium urate monohydrate (MSU) crystals have remarkable inflammatory potential. However, gouty inflammation is spontaneously self-limited, an occurrence recognized since antiquity. Gouty synovitis is driven and sustained by neutrophil influx. Importantly, macrophage phagocytosis of apoptotic (but not necrotic) neutrophils is antiinflammatory. Therefore, we tested the hypothesis that efficient clearance of apoptotic neutrophils by macrophages is one of the factors that restrains the progression of gouty inflammation. Macrophage expression of transglutaminase 2 (TG2), a multifunctional protein with reciprocally regulated transamidation and purine nucleotidebinding activities, promotes apoptotic leukocyte uptake.In this study, we tested the specific role of macrophage TG2 expression in MSU crystal-induced inflammation. Methods. We studied MSU crystal-induced peritonitis in TG2؊/؊ and congenic TG2 ؉/؉ mice. We also studied the effects of TG2 on apoptotic cell uptake by cultured macrophages.Results. TG2 ؊/؊ mice demonstrated more progressive neutrophilic accumulation than did TG2 ؉/؉ mice, which was associated with delayed clearance of apoptotic neutrophils during MSU crystal-induced peritonitis. We observed defective phagocytosis of apoptotic leukocytes by TG2 ؊/؊ peritoneal macrophages, which was corrected by soluble extracellular TG2. Transamidation catalytic activity of TG2 was not required to mediate macrophage uptake of apoptotic leukocytes. In contrast, the TG2 nucleotide binding site residue K173 was critical for this TG2 function. TG2 bound to GDP, ADP, or ATP (but not to GTP) rescued defective apoptotic leukocyte uptake by TG2 ؊/؊ macrophages. Conclusion. Enhancement of apoptotic neutrophil uptake by macrophage-derived TG2 restrains gout-like neutrophilic peritoneal inflammation. Differential binding of TG2 by purine nucleotides may contribute to clinical variability in the extent and duration of gouty inflammation.In acute gouty arthritis, monosodium urate monohydrate (MSU) crystal deposits in joints trigger inflammation; this process is largely dependent on neutrophil recruitment and proinflammatory mediator generation by resident cells in the joint and by recruited phagocytes (1,2). The capacity of MSU crystals to engage plasma membrane and intracellular innate immune pattern-recognition receptors (Toll-like receptor 2 [TLR-2] and TLR-4, and the NALP3 inflammasome, respectively) modulates crystal inflammatory potential (3-5), as do changes in plasma proteins and complement components that directly interact with MSU crystals (6-8). Despite the remarkable capacity of MSU crystals to induce multiple mediators of inflammation (1,8), self-limitation of the acute gouty attack, typically culminating in spontaneous resolution within 1-2 weeks, has been recognized for more than 2 millenia (8).Natural mechanisms limiting acute gouty inflammation include antiinflammatory disposal of MSU crystals through phagocytosis by mature macrophages, associated with generation of antiinflammatory transforming Dr.

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Macrophages: Biology and Role in the Pathology of Diseases

Biswas

Mantovani

2014

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Macrophage interaction in different contextsand tissue distribution. a Macrophages challenged with Aspergillus fumigatus conidia; b Macrophage (red) interaction with matrix (green); c-d Internalization of West Nile Virus dsRNA (cyan/green) by macrophages; e Tumor-stroma interaction showing tumor associated macrophages (yellow) in pancreatic ductal carcinoma. a-e Courtesy: Andrea Doni (Istituto Clinico Humanitas, Rozzano, Italy); f Yolk sac macrophage; g Lung macrophage; h Brain macrophage (Microglia); i Splenic macrophage. f-i

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Involvement of MIP-2 and CXCR2 in neutrophil infiltration following injection of late apoptotic cells into the peritoneal cavity

Cited by 20 publications

References 36 publications

Neutrophils Accelerate Macrophage-Mediated Digestion of Apoptotic Cells In Vivo as Well as In Vitro

Neutrophils Accelerate Macrophage-Mediated Digestion of Apoptotic Cells In Vivo as Well as In Vitro

Transglutaminase 2 limits murine peritoneal acute gout‐like inflammation by regulating macrophage clearance of apoptotic neutrophils

Macrophages: Biology and Role in the Pathology of Diseases

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