Critical Role of L-Selectin and Histamine H4 Receptor in Zymosan-Induced Neutrophil Recruitment from the Bone Marrow: Comparison with Carrageenan

Abstract

Zymosan and carrageenan represent two inflammatory stimuli leading to significant neutrophilia when injected into mice. Despite several similarities between the two proinflammatory agents, the mechanisms leading to neutrophil influx into the site of stimulus injection are unclear. As demonstrated by antibody (Ab) studies directed against adhesion molecules, L-selectin was pivotal for zymosan-induced but not carrageenan-induced pleurisy. Zymosan but not carrageenan injection into the pleural cavity caused blood neutrophilia and significant release of neutrophils from the bone marrow, events that were inhibited by anti-L-selectin but not anti-Mac-1 Ab pretreatment. Pertussis toxin, known to regulate cell efflux, abrogated both zymosanand carrageenan-induced pleurisy, but only zymosan-induced neutrophil release from the bone marrow. Dexamethasone, known to inhibit pleurisy induced by either stimulus, had no effect on bone marrow neutrophil numbers. The G i/o G proteincoupled H 4 histamine receptor is highly expressed in the bone marrow and on leukocytes and plays an important role in zymosan-induced pleurisy in vivo. Zymosan-triggered neutrophil release from bone marrow was abrogated by pretreatment of mice with thioperamide, a known H 3/4 receptor antagonist, whereas H 1 and H 2 receptor antagonists had no effect. Moreover, histamine itself, when injected intravenously, led to a similar time-and dose-dependent decrease of neutrophil numbers in the bone marrow that was inhibited by thioperamide. Because the H 3 receptor is not expressed on neutrophils, these findings indicate that both H 4 and L-selectin regulate zymosaninduced neutrophil release from bone marrow and subsequent infiltration in the pleurisy model. Acute inflammation can be experimentally induced by numerous stimuli (for example, lipopolysaccharides, phorbol esters, zymosan, and carrageenan) and is orchestrated by a complex cellular and biochemical network that involves a multitude of cell types and mediators. Due to the involvement of a high number of molecular players these models are widely used to screen for the efficacy of novel anti-inflammatory drug candidates.To experimentally induce leukocyte trafficking, carrageenan (sulfated polyanionic polysaccharide) and zymosan have become two commonly used inflammatory agents (Ohishi, 1997). Carrageenan-induced pleurisy is an experimental model of acute inflammation characterized by the migration of phagocytic cells. Polymorphonuclear leukocytes are the predominant cell type infiltrating the pleural cavity within the first 12 h after carrageenan injection. Later, polymorphonuclear cells disappear and are replaced by migrating mononuclear cells, which differentiate into macrophages and dominate the reaction up to its resolution at 48 h (Tomlinson et al., 1994;Willis et al., 1996). These inflammatory cells synthesize and release various mediators of inflammation, among which the kallirein-kinin system and prostaglandins play a pivotal role. Inhibitors of cyclooxygenase, kallikreinkinin, and brady...

Cyclosporin A inhibits CD11a/CD18 adhesion molecules due to inhibition of TNF-α and IL-1β levels in the mouse model of pleurisy induced by carrageenan

“…In this present work, using the same experimental model, we have demonstrated that CsA significantly inhibits the heterodimer CD11a/CD18 in the lungs. Our results are in accordance with Takeshita et al 8 who has also demonstrated that CD11a/ CD18 is the most important protein adhesion molecule involved in the leukocyte migration from blood and other tissue compartments to the pleural cavity and lungs in the mouse model of pleurisy induced by carrageenan.…”

“…1,5 In this context, Wilson et al 6 and also Carlos and Harlan 7 had demonstrated that CD11a/ CD18 is an important adhesion molecule involved in the leukocyte chemotaxis during the inflammatory process. Further, Takeshita et al 8 had also shown that this heterodimer protein is the most important adhesion molecule involved in the leukocyte influx at the site of the inflammatory reaction.…”

Does the Histamine H₄ Receptor Have a Pro- or Anti-Inflammatory Role in Murine Bronchial Asthma?

“…experimental mouse models comprising those for airway inflammation [9,10] , pruritus [11][12][13] , and peritonitis [14][15][16] . These models mostly rely on the use of the dual H 3 R/H 4 R antagonist thioperamide [14,15] , the H 4 R-selective antagonist JNJ 7777120 (1-[(5-chloro-1H-indole-2-yl)carbonyl]-4-methylperazine) [16] , the assumed H 4 R-selective agonist 4-methylhistamine (4MeHA) [17] , or on the H 4 R -/-mouse [8] . All of the above-mentioned mouse-based studies point to a pro-inflammatory function of H 4 R, since disease symptoms were ameliorated by treating the animals with H 4 R-antagonistic JNJ 7777120 or thioperamide or were reduced in H 4 R -/-mice.…”

Involvement of histamine receptors in the atypical antipsychotic profile of clozapine: a reassessment in vitro and in vivo

“…Murine and human progenitor cell populations express H 4 Rs and respond to its agonists by reduced cell cycle progression (Petit-Bertron et al 2009). Moreover, H 4 R activation increases neutrophil release from bone marrow (Takeshita et al 2004) and NDMC mimics clozapine not only at H 4 Rs but also on hematotoxicity (Gerson et al 1994). Therefore, even if it may not be sufficient by itself, H 4 R activation might synergize with other processes to promote and/or worsen the hematopoietic effets of clozapine.…”