Macrophages cultured in vitro release leukotriene B4 and neutrophil attractant/activation protein (interleukin 8) sequentially in response to stimulation with lipopolysaccharide and zymosan.

Rankin, John A.; Sylvester, Ilona; Smith, Sharon; Yoshimura, Teizo; Leonard, Edward J.

doi:10.1172/jci114875

Cited by 113 publications

(54 citation statements)

References 48 publications

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“…LPS was also reported to increase LTB 4 production in both cell types (46,47). Therefore, neutrophils and macrophages may be other sources of LTB 4 in the bone marrow of mice suffering from bone resorption diseases.…”

Section: Discussionmentioning

confidence: 97%

A distinctive role of the leukotriene B ₄ receptor BLT1 in osteoclastic activity during bone loss

Hikiji

Ishii

Yokomizo

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Although leukotriene B4 (LTB4) is produced in various inflammatory diseases, its functions in bone metabolism remain unknown. Using mice deficient in the high-affinity LTB4 receptor BLT1, we evaluated the roles of BLT1 in the development of two bone resorption models, namely bone loss induced by ovariectomy and lipopolysaccharide. Through observations of bone mineral contents and bone morphometric parameters, we found that bone resorption in both models was significantly attenuated in BLT1-deficient mice. Furthermore, osteoclasts from BLT1-deficient mice showed reduced calcium resorption activities compared with wild-type osteoclasts. Osteoclasts expressed BLT1, but not the low-affinity LTB4 receptor BLT2, and produced LTB4. LTB4 changed the cell morphology of osteoclasts through the BLT1-Gi protein-Rac1 signaling pathway. Given the causal relationship between osteoclast morphology and osteoclastic activity, these findings suggest that autocrine/paracrine LTB4 increases the osteoclastic activity through the BLT1-Gi protein-Rac1 signaling pathway. Inhibition of BLT1 functions may represent a strategy for preventing bone resorption diseases.bone remodeling ͉ G protein-coupled receptor ͉ knockout mice ͉ lipid mediator ͉ osteoporosis ͉ L eukotriene B 4 (LTB 4 ), a metabolite of arachidonic acid, is a potent lipid mediator with various biological activities toward neutrophils and differentiated T cells, including chemotaxis, degranulation, and production of superoxide anions (1, 2). These actions of LTB 4 are mediated by specific cell surface receptors (BLTs). We previously cloned two distinct BLTs, BLT1 and BLT2 (3,4). BLT1 is a high-affinity receptor that mediates the inhibition of adenylate cyclase and calcium entry by coupling with the Gi-and Gq-classes of G proteins (5). BLT2 transduces comparable intracellular signals but has a lower affinity to LTB 4 (5). Although several hydroxyeicosatetraenoic acids were found to activate BLT2 (6), we recently identified 12(S)-hydroxyheptadeca-5Z, 8E, 10E-trienoic acid (12-HHT) as a very potent endogenous ligand for BLT2 (7). LTB 4 is produced in inf lammatory diseases such as psoriasis (8), bronchial asthma (9), ulcerative colitis (10), postischemic tissue injuries (11), and rheumatoid arthritis (12-15).Bone remodeling consists of old bone resorption by osteoclasts and new bone deposition by osteoblasts. Osteoclasts and osteoblasts participate in bone remodeling under the control of many hormones, cytokines (16,17), and autacoids, including lipid mediators (18). The effects of LTB 4 on bone resorption were investigated using organ cultures of mouse calvariae (19,20). LTB 4 enhanced calcium efflux from the mouse calvariae, suggesting that LTB 4 stimulates bone resorption (19). LTB 4 increased the formation of resorption pits by osteoclasts in rat bone tissues (20), suggesting that LTB 4 modulates bone resorption by increasing the number and/or activity of osteoclasts. However, few reports have provided definitive biochemical information about the mRNA/protein expression and ...

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Section: Discussionmentioning

confidence: 97%

A distinctive role of the leukotriene B ₄ receptor BLT1 in osteoclastic activity during bone loss

Hikiji

Ishii

Yokomizo

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…During the inflammatory response, neutrophil migration and activation result mainly from the release of chemoattractants by resident cells, such as macrophages, mast cells or lymphocytes [38][39][40][41]. The neutrophil chemoattractant factors include TNF-a, IL-1b, plateletactivating factor (PAF), C5a, leukotriene B4 (LTB 4 ) and a variety of chemokines, including IL-8, growth-related oncogene-alpha (GRO-a), MIP-1a and stromal cellderived factor 1 (SDF-1) [42][43][44].…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, the efficacy of the so-called disease modifying anti-inflammatory drugs in several inflammatory diseases, such as rheumatoid arthritis is usually associated with their ability to decrease neutrophil influx into the inflammatory site [36,37]. Therefore, strategies to limit neutrophil trafficking and/or activation have received attention as potential alternatives in the treatment of these diseases.During the inflammatory response, neutrophil migration and activation result mainly from the release of chemoattractants by resident cells, such as macrophages, mast cells or lymphocytes [38][39][40][41]. The neutrophil chemoattractant factors include TNF-a, IL-1b, plateletactivating factor (PAF), C5a, leukotriene B4 (LTB 4 ) and a variety of chemokines, including IL-8, growth-related oncogene-alpha (GRO-a), MIP-1a and stromal cellderived factor 1 (SDF-1) [42][43][44].…”

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confidence: 99%

Effect of salivary gland extract ofLeishmania vector,Lutzomyia longipalpis, on leukocyte migration in OVA-induced immune peritonitis

Monteiro¹,

Nogueira²,

Souza³

et al. 2005

Eur. J. Immunol.

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Salivary gland extracts (SGE) from Lutzomyia longipalpis potentate L. major infection by inducing a Th2 immune response. However, the effect of SGE on the effector phase of immune response is not known. Herein, we demonstrate that SGE inhibited neutrophil migration in ovalbumin (OVA)-induced peritonitis in immunized mice. SGE pretreatment of mice inhibited OVA-induced CD4 + and CD8 + T lymphocyte migration. The OVA-induced production of TNF-a, IL-1b and leukotriene B4 (LTB 4 ), neutrophil chemotactic mediators in this model, were inhibited by SGE. On the other hand, SGE enhanced production of IL-10 and IL-4. In naive mice, SGE also blocked LTB 4 -induced neutrophil migration, but not that induced fMLP. Moreover, co-incubation of LTB 4 (but not fMLP, TNF-a and MIP-1a) with SGE inhibited the ability of LTB 4 to induce neutrophil migration in vivo and in vitro. Altogether, the results suggest that SGE has anti-inflammatory properties that are associated with inhibition of TNF-a and LTB 4 production and/or with the neutrophil chemotactic activity of LTB 4 . The effectiveness of SGE in inhibiting neutrophil migration and inflammatory mediators release in a Th1 immune inflammatory response model reinforces the need for isolation of the compounds responsible for these activities, which could be used as prototypes for the development new anti-inflammatory drugs. IntroductionParticipation of vector saliva in disease transmission has long been recognized. Saliva inoculated during blood feeding modulates the immune response allowing the infection to become established [1][2][3]. On the other hand, anti-vector saliva immunity may protect the host against some vector-borne diseases [4][5][6][7]. In leishmaniasis, there is evidence that the saliva of the vectors Lutzomyia and Phlebotomus contains substances with immunosuppressor, vasodilatator, anti-platelet and anticlotting activities [8][9][10][11][12][13]. In addition to increasing the hemorrhagic pool where sand flies feed [8,14], salivary components also induce host immunosuppression, which is fundamental for the establishment of Leishmania infection [10,[15][16][17][18][19] production and antigen presentation by infected macrophages [20][21][22]. Furthermore, they inhibit Th1 induction, enhancing the Th2-type response with an increase of IL-4 and IL-10 in the infection [23][24][25]. A predominance of the Th1 response has been reported in several inflammatory diseases, including rheumatoid arthritis, Crohn's disease, glomerulonephritis, and immune vasculitis [26][27][28][29]. The participation of neutrophils in the pathogenesis of tissue lesions in these diseases has long been recognized [30][31][32][33]. These cells are important sources of substances that promote tissue damage, such as reactive oxygen and nitrogen species, lysosomal enzymes and metalloproteases [34,35]. Indeed, the efficacy of the so-called disease modifying anti-inflammatory drugs in several inflammatory diseases, such as rheumatoid arthritis is usually associated with their ability to decrease neutro...

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“…LTB 4 is a lipoxygenase product of arachidonic acid metabolism and is generated primarily by polymorphonuclear (3,12) and mononuclear phagocytes (36). It has been identified, in chamber models (25) and other models of intravital microscopy (2,20), as a key mediator of leukocyte-endothelial cell interaction in intact organisms after ischemia-reperfusion injury and as a potent chemoattractant responsible for the recruitment of neutrophils to the site of inflammation (34).…”

Section: Discussionmentioning

confidence: 99%

Paradoxical attenuation of leukocyte rolling in response to ischemia- reperfusion and extracorporeal blood circulation in inflamed tissue

Schäfer¹,

Sehrt²,

Kamler³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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In contrast to acute preparations such as the exteriorized mesentery or the cremaster muscle, chronically instrumented chamber models allow one to study the microcirculation under "physiological" conditions, i.e., in the absence of trauma-induced leukocyte rolling along the venular endothelium. To underscore the importance of studying the naive microcirculation, we implanted titanium dorsal skinfold chambers in hamsters and used intravital fluorescence microscopy to study venular leukocyte rolling in response to ischemia-reperfusion injury or extracorporeal blood circulation. The experiments were performed in chambers that fulfilled all well-established criteria for a physiological microcirculation as well as in chambers that showed various extents of leukocyte rolling due to trauma, hemorrhage, or inflammation. In ideal chambers with a physiological microcirculation (Ͻ30 rolling leukocytes/mm vessel circumference in 30 s), ischemia-reperfusion injury and extracorporeal blood circulation significantly stimulated leukocyte rolling along the venular endothelium and, subsequently, firm leukocyte adhesion. In contrast, both stimuli failed to elicit leukocyte rolling in borderline chambers (30 -100 leukocytes/mm), and in blatantly inflamed chambers with yet higher numbers of rolling leukocytes at baseline (Ͼ100 leukocytes/mm), we observed a paradoxical reduction of leukocyte rolling after ischemia-reperfusion injury or extracorporeal blood circulation. A similar effect was observed when we superfused leukotriene B 4 (LTB4) onto the chamber tissue. The initial increase in leukocyte rolling in response to an LTB 4 challenge was reversed by a second superfusion 90 min later. These observations underscore 1) the benefit of studying leukocyte-endothelial cell interaction in chronically instrumented chamber models and 2) the necessity to strictly adhere to well-established criteria of a physiological microcirculation. leukotriene B 4; animal model; intravital microscopy THE MULTISTEP CONCEPT of leukocyte-endothelial cell interaction proposes early leukocyte tethering and rolling along the endothelial wall followed by firm leukocyte adhesion and transendothelial emigration; each consecutive step involves distinct adhesion molecules and distinct chemoattractant and/or adhesion-promoting mediators (5,21,23,29). It is widely established that leukocyte rolling along the endothelium constitutes a prerequisite for subsequent leukocyte adhesion and emigration (22). However, Kanwar and co-workers (21) identified an enormous redundancy in this system: even an inhibition of leukocyte rolling by Ͼ90% with fucoidin or selectin antagonists exerted no significant effect on subsequent firm leukocyte adhesion.In intact animal organisms, the study of leukocyte-endothelium interaction can be accomplished by intravital microscopy on acutely prepared tissues (e.g., hamster cheek pouch, cremaster muscle, and exteriorized mesentery) or on chronically instrumented tissues [e.g., the dorsal skinfold chamber model in hamsters (10, 28) and mice (27)...

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Macrophages cultured in vitro release leukotriene B4 and neutrophil attractant/activation protein (interleukin 8) sequentially in response to stimulation with lipopolysaccharide and zymosan.

Cited by 113 publications

References 48 publications

A distinctive role of the leukotriene B ₄ receptor BLT1 in osteoclastic activity during bone loss

A distinctive role of the leukotriene B ₄ receptor BLT1 in osteoclastic activity during bone loss

Effect of salivary gland extract ofLeishmania vector,Lutzomyia longipalpis, on leukocyte migration in OVA-induced immune peritonitis

Paradoxical attenuation of leukocyte rolling in response to ischemia- reperfusion and extracorporeal blood circulation in inflamed tissue

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Macrophages cultured in vitro release leukotriene B4 and neutrophil attractant/activation protein (interleukin 8) sequentially in response to stimulation with lipopolysaccharide and zymosan.

Cited by 113 publications

References 48 publications

A distinctive role of the leukotriene B 4 receptor BLT1 in osteoclastic activity during bone loss

A distinctive role of the leukotriene B 4 receptor BLT1 in osteoclastic activity during bone loss

Effect of salivary gland extract ofLeishmania vector,Lutzomyia longipalpis, on leukocyte migration in OVA-induced immune peritonitis

Paradoxical attenuation of leukocyte rolling in response to ischemia- reperfusion and extracorporeal blood circulation in inflamed tissue

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A distinctive role of the leukotriene B ₄ receptor BLT1 in osteoclastic activity during bone loss

A distinctive role of the leukotriene B ₄ receptor BLT1 in osteoclastic activity during bone loss