Contribution of CD54 to human eosinophil and neutrophil superoxide production

Abstract

We have reported that CD54 on eosinophils is involved in eosinophil degranulation. However, the role of CD54 in eosinophil and neutrophil superoxide production is still uncertain. We assessed the effect of CD54 on eosinophils and neutrophils in recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF)- or phorbol myristate acetate (PMA)-induced superoxide production through CD18. Anti-CD54 monoclonal antibody attenuated leukocyte aggregation and superoxide production of rGM-CSF- or PMA-stimulated neutrophils and PMA-stimulated eosinophils. Anti-CD18 monoclonal antibody or theophylline attenuated superoxide production of eosinophils and neutrophils stimulated by either stimuli. Flow cytometric analysis demonstrated CD54 expression on freshly isolated neutrophils but not on freshly isolated eosinophils. CD54 newly expressed on eosinophils reached its peak expression 30 min after PMA stimulation. The increase in CD18 and CD54 expression on neutrophils caused by rGM-CSF stimulation was partially inhibited by theophylline. These data demonstrated that CD54 and CD18 interaction of eosinophils or neutrophils is involved in superoxide production and that the inhibition of superoxide production by theophylline may be at least partly due to the inhibition of CD54 and CD18.

ICAM-1–expressing neutrophils exhibit enhanced effector functions in murine models of endotoxemia

“…Because the profile of stimuli that induce neutrophil ICAM-1 are pathogen-derived and/or are commonly released under conditions of infection, we hypothesized that elevated neutrophil ICAM-1 may represent a physiological response associated with pathogen clearance. Indeed, although neutrophil ICAM-1 has to date been largely investigated in the context of neutrophil-neutrophil adhesion, aggregation, 26,28 and neutrophil interactions with other components of the immune response, 21 here we made the novel observation that neutrophil ICAM-1 supports an efficient phagocytosis response and is also associated with enhanced ROS generation. Although endothelial and epithelial cell ICAM-1 have been shown to support neutrophil phagocytosis by providing costimulatory signals through neutrophil integrins, [43][44][45] to our knowledge this is the first report on the involvement of neutrophil ICAM-1 in neutrophil phagocytosis.…”

“…58 Of relevance, ICAM-1 blockade inhibits production of ROS by neutrophils in response to granulocyte macrophage colony-stimulating factor or PMA, 28 and ICAM-1 crosslinking has been linked to ROS generation and signaling in monocytes, 59 indicating a broad role for myeloid cell ICAM-1 signaling as a regulator of superoxide anion generation. Finally, because neutrophils constitutively express the key ICAM-1 ligands, b2 integrins LFA-1 and Mac-1, ICAM-1-mediated neutrophil adhesion/aggregation may trigger ROS generation in an adhesion-dependent manner, as previously detailed.…”

“…17,23 Furthermore, there are indications that granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, LPS, TNF, bacterial lipoprotein, and Staphylococcus aureus can induce expression of ICAM-1 on human neutrophils in vitro. 16,[24][25][26][27] In terms of its physiological role, neutrophil ICAM-1 has been linked to cellular aggregation, increased generation of reactive oxygen species (ROS) 26,28 and in supporting interactions with other components of the immune system. 21 Despite these scant reports, little is known about the mechanisms through which ICAM-1 is expressed on neutrophils and its potential pathophysiological functions.…”

Cross-Talk between ICAM-1 and GM-CSF Receptor Signaling Modulates Eosinophil Survival and Activation

“…The importance of ICAM-1 for eosinophil functions other than locomotion was suggested in several reports. First, in GM-CSF-activated eosinophils, a blockade of ICAM-1 inhibited release of eosinophil-derived neurotoxin and superoxide production (17,40). Second, adherence of eosinophils to fibronectin, an ICAM-1-ligand, significantly up-regulated the release of cytotoxic mediators such as EDN, EPO, and leukotriene C 4 (4 -6, 15, 16), suggesting that cytokine-induced signaling and signaling from ICAM-1 do interact.…”

“…Significantly, however, lung tissue eosinophils do express ICAM-1 (12)(13)(14). ICAM-1 was indicated as a potential modulator of IL-5-induced activation of eosinophils because their adherence to fibronectin significantly up-regulated the release of cytotoxic mediators such as eosinophil-derived neurotoxin, eosinophil peroxidase (EPO), 3 and leukotriene C 4 (6,(15)(16)(17). Furthermore, blockade of ICAM-1 in GM-CSF-activated eosinophils inhibited the release of EPO (6).…”