Immunocytochemical Identification of Azurophilic and Specific Granule Markers in the Giant Granules of Chediak-Higashi Neutrophils

Rausch, PG; Pryzwansky, Katherine B.; Spitznagel, John K.

doi:10.1056/nejm197803302981301

Cited by 91 publications

(42 citation statements)

References 20 publications

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“…Furthermore, morphological features indicated the fusion of specific granules with giant granules [1]. This was in keeping with the findings by Rausch et al [12], who demonstrated colocalization of lactoferrin and myeloperoxidase in giant granules by immunofluorescence double labeling with the use of light microscopy. While the former investigation lacked precise identification of specific granules, the latter may suffer from insufficient resolution for firm conclusions to be drawn.…”

Section: Discussionsupporting

confidence: 87%

Giant granules of neutrophils in Chediak-Higashi syndrome are derived from azurophil granules but not from specific and gelatinase granules

Kjeldsen

Calafat

Borregaard

1998

Journal of Leukocyte Biology

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The abnormal giant granules of ChediakHigashi syndrome (CHS) neutrophils in humans are thought to be derived from both azurophil and specific granules, whereas the presence of gelatinase granules and their contribution to giant granule formation has not been investigated previously. We have examined the ultrastructure and mobilization of neutrophil granules from a patient with CHS by immunogold electron microscopy and exocytosis experiments of isolated leukocytes. The giant granules contained the azurophil granule components myeloperoxidase and CD63. We found no evidence of involvement of specific or gelatinase granules in the formation of giant granules because lactoferrin and gelatinase were contained in normalappearing peroxidase-negative granules. On stimulation of leukocytes with N-formyl-methionyl-leucylphenylalanine and the calcium ionophore, ionomycin, there was a diminished exocytosis of myeloperoxidase in CHS compared with a healthy control, indicating a lack of mobilization of the giant granules. On the other hand, there was a normal or augmented release of lactoferrin and gelatinase in CHS neutrophils, with gelatinase granules being the most easily mobilized, as known from normal neutrophils. In conclusion, giant granules from CHS neutrophils originate from azurophil granules but not from the specific and gelatinase granules. J. Leukoc. Biol. 64: 72-77; 1998.

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Section: Discussionsupporting

confidence: 87%

Giant granules of neutrophils in Chediak-Higashi syndrome are derived from azurophil granules but not from specific and gelatinase granules

Kjeldsen

Calafat

Borregaard

1998

Journal of Leukocyte Biology

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“…Myeloperoxidase (MPO) is a heme-containing peroxidase that constitutes the most abundant component in azurophilic granules in neutrophils, has often been used as an histopathological marker for neutrophils [13,14], and has recently been used as an in vivo marker of brain inflammation [15].…”

Section: Introductionmentioning

confidence: 99%

Decreased myeloperoxidase expressing cells in the aged rat brain after excitotoxic damage

Campuzano¹,

Castillo-Ruiz²,

Acarín³

et al. 2011

Experimental Gerontology

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Brain aging is associated to several morphological and functional alterations that influence the evolution and outcome of CNS damage. Acute brain injury such as an excitotoxic insult induces initial tissue damage followed by associated inflammation and oxidative stress, partly attributed to neutrophil recruitment and the expression of oxidative enzymes such as myeloperoxidase (MPO), among others. However, to date, very few studies have focused on how age can influence neutrophil infiltration after acute brain damage. Therefore, to evaluate the age-dependent pattern of neutrophil cell infiltration following an excitotoxic injury, intrastriatal injection of Nmethyl-D-aspartate was performed in young and aged male Wistar rats. Animals were sacrificed at different times between 12 hours post-lesion (hpl) to 14 days post-lesion (dpl). Cryostat sections were processed for myeloperoxidase (MPO) immunohistochemistry, and double labeling for either neuronal cells (NeuN), astrocytes (GFAP), perivascular macrophages (ED-2), or microglia/macrophages (tomato lectin histochemistry). Our observations showed that MPO+ cells were observed in the injured striatum from 12 hpl (when maximum values were found) until 7 dpl, when cell density was strongly diminished. However, at all survival times analyzed, the overall density of MPO+ cells was lower in the aged versus the adult injured striatum. MPO+ cells were mainly identified as neutrophils (especially at 12 hpl and 1 dpl), but it should be noted that MPO+ neurons and microglia/macrophages were also found. MPO+ neurons were most commonly observed at 12 hpl and reduced in the aged. MPO+ microglia/macrophages were the main population expressing MPO from 3 dpl, when density was also reduced in aged subjects.These results point to neutrophil infiltration as another important factor contributing to the different response of the adult and aged brain to damage, highlighting the need of using aged animals for the study of acute agerelated brain insults.

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“…Myeloperoxidase (MPO) is the most abundant component in azurophilic granules in neutrophils and has often been used as a histopathological marker for neutrophils (6). It is also expressed in the myeloid line, especially in monocytes and macrophages/microglia.…”

mentioning

confidence: 99%

Tracking the inflammatory response in stroke in vivo by sensing the enzyme myeloperoxidase

Breckwoldt

Chen

Stangenberg³

et al. 2008

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

279

240

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Inflammation can extend ischemic brain injury and adversely affect outcome in experimental animal models. A key difficulty in translating animal studies to humans is the lack of a definitive method to confirm and track inflammation in the brain in vivo. Myeloperoxidase (MPO), a key inflammatory enzyme secreted by activated neutrophils and macrophages/microglia, can generate highly reactive oxygen species to cause additional damage in cerebral ischemia. We report here that a functional, enzyme-activatable MRI agent can accurately track the oxidative activity of MPO noninvasively in stroke in living animals. We found that MPO is widely distributed in ischemic tissues, correlates positively with infarct size, and is detected even 3 weeks postinfarction. The peak level of MPO activity, determined by activation of the MPO-sensing agent in vivo and confirmed by MPO activity and quantitative RT-PCR assays, occurred on day 3 after ischemia. Both neutrophils and macrophages/microglia contribute to secrete MPO in the ischemic brain, although neutrophils peak earlier (days 1-3) whereas macrophages/microglia are most abundant later (days 3-7). In contrast to the conventional MRI agent diethylenetriaminepentatacetate gadolinium, which reports blood-brain barrier disruption, MPO imaging is able to additionally track MPO activity and confirm inflammation on the molecular level in vivo, information that was previously only possible to obtain on ex vivo brain sections and impossible to assess in living human patients. Our findings could allow efficient noninvasive serial screening of therapies targeting inflammation and the use of MPO imaging as an imaging biomarker to risk-stratify patients.inflammation ͉ ischemia ͉ molecular imaging ͉ MRI ͉ brain

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Immunocytochemical Identification of Azurophilic and Specific Granule Markers in the Giant Granules of Chediak-Higashi Neutrophils

Cited by 91 publications

References 20 publications

Giant granules of neutrophils in Chediak-Higashi syndrome are derived from azurophil granules but not from specific and gelatinase granules

Giant granules of neutrophils in Chediak-Higashi syndrome are derived from azurophil granules but not from specific and gelatinase granules

Decreased myeloperoxidase expressing cells in the aged rat brain after excitotoxic damage

Tracking the inflammatory response in stroke in vivo by sensing the enzyme myeloperoxidase

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