Hemin, a heme oxygenase substrate analog, inhibits the cell surface expression of CD11b and CD66b on human neutrophils

Andersson, Jens; Egesten, Arne; Cardell, Lars-Olaf

doi:10.1034/j.1398-9995.2002.23593.x

Cited by 15 publications

(8 citation statements)

References 50 publications

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“…Neutrophils expressing higher levels of adhesion molecules would preferentially migrate to the lungs and nose following allergic challenge, and therefore the cells remaining would consist of a population with lower surface levels of adhesion molecules. These data suggest that these adhesion molecules are key to neutrophil recruitment to the lungs and nose in allergic processes [17], [28], [29], [30], [31]. In addition to the presented data, we have previously shown that the activation of neutrophils from allergic patient through the IgE-receptor galectin-3 induces the downmodulation of CD62L expression and the release of key inflammatory mediators [8], [14].…”

Section: Discussionsupporting

confidence: 63%

Immunotherapy Reduces Allergen-Mediated CD66b Expression and Myeloperoxidase Levels on Human Neutrophils from Allergic Patients

et al. 2014

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CD66b is a member of the carcinoembryonic antigen family, which mediates the adhesion between neutrophils and to endothelial cells. Allergen-specific immunotherapy is widely used to treat allergic diseases, and the molecular mechanisms underlying this therapy are poorly understood. The present work was undertaken to analyze A) the in vitro effect of allergens and immunotherapy on cell-surface CD66b expression of neutrophils from patients with allergic asthma and rhinitis and B) the in vivo effect of immunotherapy on cell-surface CD66b expression of neutrophils from nasal lavage fluid during the spring season. Myeloperoxidase expression and activity was also analyzed in nasal lavage fluid as a general marker of neutrophil activation.ResultsCD66b cell-surface expression is upregulated in vitro in response to allergens, and significantly reduced by immunotherapy (p<0.001). Myeloperoxidase activity in nasal lavage fluid was also significantly reduced by immunotherapy, as were the neutrophil cell-surface expression of CD66b and myeloperoxidase (p<0.001). Interestingly, CD66b expression was higher in neutrophils from nasal lavage fluid than those from peripheral blood, and immunotherapy reduced the number of CD66+MPO+ cells in nasal lavage fluid. Thus, immunotherapy positive effects might, at least in part, be mediated by the negative regulation of the CD66b and myeloperoxidase activity in human neutrophils.

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Section: Discussionsupporting

confidence: 63%

Immunotherapy Reduces Allergen-Mediated CD66b Expression and Myeloperoxidase Levels on Human Neutrophils from Allergic Patients

et al. 2014

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“…The significance of the catalytic activity of the HO system is accentuated by the fact that heme itself is an effector molecule that can regulate inflammatory response (Andersson et al, 2002) and activate molecular oxygen (Aust and Svingen, 1982). Collectively, the multidimensional functions of the system has lead to the current understanding that increase in cellular HO activity is a mechanism for protecting the cell against untoward stimuli such as ischemia/reperfusion insult to organs including the kidney (reviewed in Hill-Kapturczak et al, 2002).…”

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confidence: 99%

Nitric Oxide Inhibitor Nω-Nitro-l-arginine Methyl Ester Potentiates Induction of Heme Oxygenase-1 in Kidney Ischemia/Reperfusion Model: A Novel Mechanism for Regulation of the Oxygenase

Mayer

Wang²,

Maines³

2003

The Journal of Pharmacology and Experimental Therapeutics

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The biological significance of the heme oxygenase (HO) system's response to stress reflects functions of its products-CO and bile pigments. CO is a messenger molecule, whereas bile pigments are antioxidants and modulators of cell signaling. Presently, an unexpected mechanism for sustained suprainduction of renal HO-1 following ischemia/reperfusion injury is described. Inhibition of nitric-oxide synthase (NOS) activity by N -nitro-L-arginine methyl ester (L-NAME) at the resumption of reperfusion of rat kidney subjected to bilateral ischemia (30 min) was as effective as the most potent HO-1 inducer, the spin trap agent n-tert-butyl-␣-phenyl nitrone (PBN), in causing sustained suprainduction of HO-1 mRNA. PBN forms stable radicals of oxygen and nitrogen. Twenty-four hours after reperfusion, HO-1 mRNA measured ϳ30-fold that of the control in the presence of L-NAME treatment; in its absence, the transcript increased to only ϳ5-fold. At 4 h in the presence or absence of the L-NAME HO-1, mRNA was increased by ϳ30-fold. The transcript was translated to active protein as indicated by Western blotting, immunohistochemistry, and activity analyses. L-NAME was not effective given 1 h after resumption of reperfusion. Suprainduction was restricted to the kidney and not detected in the heart and aorta; ferritin expression in the kidney was not effected. It is reasoned that in tissue directly insulted by ischemia/reperfusion, increased production of NO radicals promotes the loss of HO-1 transcript. Because the absence of NO radicals and presence of PBN had a similar effect on HO-1, we propose that suprainduction of the gene is mainly caused by O 2 radicals formed on reperfusion. Inhibition of NOS is potentially useful for sustained induction of HO-1 in organs that will be subjected to oxidative-stress insult.Until recently, cellular degradation of the heme molecule (Fe-protoporphyrin IX, hemin) by the heme oxygenase (HO) system was viewed primarily in context of a mechanism for dispensing senescent heme compounds and recycling of iron. Other products formed in the course of catalytic activity of the HO system-CO and bile pigments-were solely considered in context of their toxicity. The view regarding the HO system dramatically changed when heme degradation products were identified as vital regulating factors in the cell. Compelling evidence has been presented showing that CO, in analogy with NO, is a signal molecule for the generation of cGMP and plays a role in neuronal signaling, vascular tone relaxation, as well as anti-apoptotic and apoptotic gene expression (Morita et al

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“…The expression of P and E selectin in different regional vascular beds of the rat was increased in lipopolysaccharide-treated animals, and the overexpression of selectins was decreased in a similar fashion by pretreatment with hemin, bilirubin, biliverdin, but not by exogenous CO gas (34). CO is endogenously produced in the upper respiratory tract, and increased compensatory levels have been reported in allergic inflammation of the airways (35).…”

Section: Discussionmentioning

confidence: 93%

A carbon monoxide‐releasing molecule (CORM‐3) abrogates polymorphonuclear granulocyte‐induced activation of endothelial cells and mast cells

et al. 2008

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We hypothesized that circulating polymorphonuclear granulocytes (PMNs), vascular endothelial cells (ECs), and perivascular mast cells (MCs) may initiate and sustain the inflammatory response through the generation of the superoxide anion (O(2)(*-)) by PMNs primed by inflammatory stimuli, which in turn evoked the overexpression of adhesion molecules from ECs and release of histamine by MCs. To pin-point the role of carbon monoxide (CO) in curbing vascular inflammation, we studied the effect of a water-soluble CO-releasing molecule [tricarbonylchloro-glycinate-ruthenium (II); CORM-3] on an experimental model of vascular inflammation. The model consists of coincubating formyl-methionyl peptide (fMLP) -primed human PMNs with rat ECs or with rat MCs. The effects of CORM-3 were evaluated by measuring the generation of O(2)(*-) and the expression of CD11b in fMLP-primed PMNs; the expression of ICAM-1 and CD203c in ECs and MCs, respectively; and the release of histamine from MCs. Our results show that the chemotactic peptide fMLP primes PMNs to generate O(2)(*-) and overexpress CD11b, both events being central to the inflammatory process, while CORM-3 significantly decreases these events (IC(50)=1.66 microM for O(2)(*-) production; 1.20 microM for CD11b expression in human PMNs). The experiments also show that fMLP-primed PMNs increase the CD54 expression by coincubated ECs, and the expression of CD203c and the release of histamine by coincubated MCs. Once again, CORM-3 abolishes these events (IC(50)=6.78 microM for CD54 expression in ECs; 1.18 microM for CD203 expression; 1.15 microM for histamine release in MCs). Thus, CORM-3 exerts a powerful anti-inflammatory action by down-regulating the oxidative burst in PMNs, the overexpression of adhesion molecules in PMNs and ECs, the release of histamine, and the overexpression of an activation marker by MCs.

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Hemin, a heme oxygenase substrate analog, inhibits the cell surface expression of CD11b and CD66b on human neutrophils

Cited by 15 publications

References 50 publications

Immunotherapy Reduces Allergen-Mediated CD66b Expression and Myeloperoxidase Levels on Human Neutrophils from Allergic Patients

Immunotherapy Reduces Allergen-Mediated CD66b Expression and Myeloperoxidase Levels on Human Neutrophils from Allergic Patients

Nitric Oxide Inhibitor Nω-Nitro-l-arginine Methyl Ester Potentiates Induction of Heme Oxygenase-1 in Kidney Ischemia/Reperfusion Model: A Novel Mechanism for Regulation of the Oxygenase

A carbon monoxide‐releasing molecule (CORM‐3) abrogates polymorphonuclear granulocyte‐induced activation of endothelial cells and mast cells

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