Eosinophil cationic protein in peripheral blood of pediatric patients with allergic diseases

We have studied the levels of eosinophil cationic protein (ECP) and tumour necrosis factor (TNF) in peripheral blood obtained from 68 children with bronchial asthma and 11 children with atopic dermatitis. The ECP mean concentrations of the patients were 23.7 +/- 21.4 micrograms/l and 21.2 +/- 18.7 micrograms/l for bronchial asthma and atopic dermatitis respectively, which were significantly higher than the control value, 5.8 +/- 2.3 micrograms/l (P less than 0.005). TNF was unmeasurable in almost all the samples and no significant difference was observed between normal controls and asthmatic children. A significant correlation was observed between serum levels of ECP and blood eosinophil counts in both diseases (r = 0.873; P less than 0.01 and r = 0.740; P less than 0.01, respectively). However, no obvious correlation was observed between serum levels of ECP and IgE levels. ECP levels were significantly reduced by treatment and normalized in parallel with blood eosinophil counts in the patients with total IgE levels less than 800 U/ml. Irrespective of the total IgE levels, the reduction of serum ECP levels was correlated with a decrease in the number of asthmatic attacks and/or improvement of pulmonary function. These results suggest that the ECP levels in peripheral blood indicate an increased activity of eosinophil and would be a more useful marker than eosinophil counts for making clinical analyses and estimating treatment efficacy in paediatric patients with allergic diseases.     

人PFP、GrB共表达诱导喉癌Hep-2细胞凋亡的研究

目的 探讨人穿孔素(PFP)、颗粒酶B(GrB)共表达是否可以诱导人的喉癌细胞系Hep-2的凋亡及其作用的机理.方法 利用脂质体2000将PFP、GrB共表达载体pVAX1-PIG(即pVAX1-PFP-IRES-GrB)转染人喉癌Hep-2细胞,采用荧光染料Hoechst33342法、流式细胞仪(FCM)检测、透射电镜观察Hep-2细胞的凋亡情况.以激光共聚焦显微镜检测重组载体转染后的Hep-2细胞内[Ca2+];浓度的变化,并探讨其作用机理.结果 pVAX1-PIG转染组的Hep-2细胞大量凋亡且其凋亡率显著高于对照组(P＜0.05),透射电镜研究显示单个Hep-2细胞内亦出现凋亡的特征.Hep-2细胞内[Ca2+];的浓度发生了变化,且由FI值增大可知细胞胞浆内[Ca2+];的浓度升高.结论 PFP、GrB共表达能够诱导人Hep-2细胞的凋亡,且凋亡的发生与细胞胞浆内[Ca2+];的浓度升高有关.     

Phagocytosis of apoptotic eosinophils but not neutrophils by bronchial epithelial cells

BACKGROUND: We have previously demonstrated that human bronchial epithelial cells engulf apoptotic eosinophils. OBJECTIVES: To compare and contrast the phagocytic capabilities of monocyte-derived macrophage and primary airway epithelial cells for apoptotic granulocytes. RESULTS: Here we compared phagocytosis of human apoptotic eosinophils and neutrophils by small and large airway epithelial cells (SAEC and LAEC) and monocyte-derived macrophages. Confocal microscopy of F-actin staining and scanning and transmission electron microscopy revealed phagocytic cup formation around apoptotic eosinophils by airway epithelial cells (AEC) membranes with evidence of their digestion. Resting and cytokine-stimulated AEC did not recognize and ingest apoptotic neutrophils. The latter were phagocytosed by macrophages that exhibited greater ingestion of and higher capacity for, apoptotic eosinophils over apoptotic neutrophils. Cytochalasin D completely abolished uptake of apoptotic eosinophils by SAEC, LAEC or macrophage monolayers. Ligation of epithelial cell CD44 receptors for 24 h increased phagocytosis of apoptotic eosinophils by SAEC and LAEC with a potency comparable with that of IL-1. Phagocytosis was a specific receptor-mediated process involving integrin- (alphavbeta3, alphavbeta5, CD36), phosphatidylserine receptor- and lectin-dependent mechanisms. No significant differences were observed in avarice for apoptotic eosinophils by SAEC or LAEC either resting, CD44 monoclonal antibodies- or cytokine- stimulated, or in their usage and expression of recognition receptors. CONCLUSION: These findings further suggest and define an important role for the bronchial epithelium in the selective removal of apoptotic eosinophils from the airways in asthma.     

Eosinophil cationic protein and myeloperoxidase in nasal secretion as markers of inflammation in allergic rhinitis

The inflammatory component of allergic rhinitis was studied by measuring the concentration and content of eosinophil cationic protein (ECP, specific for eosinophils) and myeloperoxidase (MPO, specific for neutrophils) in samples of nasal secretion from 20 pollen-allergic subjects. All secretion samples contained measurable concentrations of both proteins. The mean ECP concentrations on two occasions without pollen exposure were 950 and 1170 micrograms/l. The ECP concentration during the pollen season without any therapy (mean 1160 micrograms/l) did not differ significantly from the baseline values, but intranasal corticosteroid therapy resulted in a significant decrease (mean 530 micrograms/l). The concentration of MPO was about 10 times higher than that of ECP, but the changes in MPO were nonsignificant throughout the observation period. An inverse correlation was found between the threshold dose in histamine challenges and the ECP level expressed either as concentration or as content. Furthermore, the ECP concentration and content 1 day after a positive allergen challenge were both significantly correlated with the strength of the challenge reaction. Measurements of ECP in nasal secretions are useful for studying the presence and activity of eosinophils in the nasal mucosa, and may prove of value in clinical investigations on patients with allergic rhinitis.     

Zonal variations in cytoskeletal element organization,mRNA and protein expression in the intervertebral disc

The intervertebral disc is important in maintaining flexibility and dissipating loads applied to the spine. The disc comprises a heterogeneous population of cells, including those of the nucleus pulposus and annulus fibrosus, which are diverse in phenotype, partly due to the different mechanical loads they experience. Several studies have implicated the cytoskeleton in mechanotransduction, but little characterization of the three major cytoskeletal elements – actin, tubulin and vimentin – in the intervertebral disc has been undertaken. In this study we show that there are differences in both the organization and the amounts of these cytoskeletal proteins across the regions of immature bovine intervertebral disc (nucleus pulposus and outer annulus fibrosus), which differs with skeletal maturity. These differences are likely to reflect the diverse mechanical characteristics of the disc regions, and the loads that they experience, i.e. tension in the annulus fibrosus and compression in the nucleus pulposus. Alterations to the organization and amount of cytoskeletal element proteins may change the ability of the cells to respond to mechanical signals, with a loss of tissue homeostasis, suggesting that the cytoskeleton has a potential role in intervertebral disc degeneration.     

Increased levels of IL-5 positive peripheral blood eosinophils and lymphocytes in mild asthmatics after allergen inhalation provocation

BACKGROUND: In allergic inflammation eosinophils and TH2-like lymphocytes are supposed to be the major effector cells and considered to contribute as cellular source of the key cytokine interleukin (IL)-5. OBJECTIVE: The purpose of this study was to enable detection of IL-5 containing leucocytes and to investigate whether the number of these cells in the blood circulation differed between healthy and asthmatics before and after allergen provocation. METHODS: The distribution of intracellular IL-5 in human peripheral blood eosinophils (PBE) and lymphocytes (PBL) has been investigated using fixation and cell membrane permeabilization with octyl-glucopyranoside, the FOG-method, and flow cytometry. The intracellular staining was performed on leucocytes without any prior purification and in vitro stimulation. The specificity of IL-5 binding to intracellular compartment of both PBE and PBL was confirmed by complete inhibition with human recombinant IL-5. RESULTS: Preformed intracellular IL-5 was detected in the main population of PBE (> 70%) in both healthy individuals and asymptomatic patients. Moreover, preformed intracellular IL-5 was also detected in 4.8% and 2.4% of PBL from healthy individuals and asymptomatic patients, respectively. There was a correlation between the absolute number of PBE and IL-5 positive PBE. In patients with pollen-related asthma, the number of IL-5 positive PBE and PBL increased significantly 24 h after an allergen inhalation provocation (P < 0.05). In the healthy control group no differences regarding IL-5 positive PBE and PBL were obtained pre- and post-allergen challenge. CONCLUSIONS: In patients with mild allergic asthma, but not in healthy individuals, allergen provocation induces an increased absolute number of IL-5 positive PBE and PBL. The reason for the relatively high number of IL-5 positive PBL is unclear, but a plausible explanation might be that other lymphocyte subsets besides CD4+ TH2 can produce IL-5. However, enumeration of IL-5 positive leucocytes may be used as an activity marker and also be a useful tool in monitoring the inflammation in asthma.     

Quantitative, rather than qualitative, differences in CD69 upregulation in human blood eosinophils upon activation with selected stimuli

BACKGROUND: The study aimed to investigate whether CD69 expression on granulocytes is subject to specific regulation by inflammatory mediators, and, if so, to identify these factors in relation to eosinophil activity markers such as the EG2 epitope and ECP release. METHODS: Peripheral blood leukocytes from healthy donors were used. The surface and intracellular distribution of CD69 was investigated with a whole-blood cell-membrane permeabilization technique, the FOG method, and flow cytometry. In vitro stimulation was performed with GM-CSF, IL-5, IL-5 plus eotaxin, LPS, and fMLP. RESULTS: A preformed intracellular pool of CD69 was demonstrated in both eosinophils and neutrophils, but not in monocytes. Almost no resting eosinophils, neutrophils, or monocytes expressed CD69 on the cell surface. However, in vitro stimulation with selected stimuli increased the proportion of CD69-positive eosinophils to various extents, with GM-CSF being the most and fMLP the least efficient stimulus. The neutrophils did not respond under these conditions. Increased expression of the EG2 epitope and initiation of degranulation preceded CD69 upregulation. CONCLUSIONS: Eosinophils and neutrophils from healthy donors have a preformed intracellular pool of CD69, which is mobilized on the cell surface on eosinophils, but not on neutrophils, to various extents by selected stimuli. Monocytes, however, do not have a preformed intracellular pool of CD69. Our data indicate that a kinetic order exists among the EG2 expression, the degranulation process, and CD69 upregulation. Due to a quantitative, rather then a qualitative, upregulation of CD69 by stimuli associated with both allergic and bacterial inflammation, CD69 may be a potential activity marker of clinical value.     

Down-regulated IL-5 receptor expression on peripheral blood eosinophils from budesonide-treated children with asthma

BACKGROUND: The expression and function of cytokine receptors on peripheral blood eosinophils (PBE) from healthy and asthmatic children are poorly characterized. METHODS: The PBE count and expression of IL-5 receptor (R) and GM-CSFR positive PBE was analyzed in nonsteroid-treated asthmatic children (n = 13), budesonide-treated asthmatic children (n = 24) and healthy children (n = 16) by flow cytometry. Alterations in intracellular EG2-epitope expression were used to measure the in vitro responsiveness of PBE to recombinant IL-5 and GM-CSF. RESULTS: The PBE count was increased (P < 0.05) in both asthmatic groups, independent of treatment, as compared to healthy children. The IL-5R expression on PBE, as well as the in vitro responsiveness of PBE to recombinant IL-5, was reduced (P < 0.05), in budesonide-treated asthmatic children compared to nonsteroid-treated asthmatic children and healthy children. The proportion of GM-CSFR positive PBE and in vitro responsiveness of PBE to recombinant GM-CSF were not different between the groups. In vitro treatment with budesonide did not down-regulate the proportion of IL-5R positive PBE. CONCLUSIONS: Budesonide-treatment of asthmatic children induces a selectively reduced IL-5R expression on PBE, concomitant with a reduced in vitro responsiveness of PBE to IL-5. We suggest that this budesonide-related down-regulation of the IL-5R might be a mechanism by which steroid treatment inhibits the action of IL-5 on eosinophil accumulation and activation in vivo.     

High dimensional analysis reveals distinct NK cell subsets but conserved response to stimulation in umbilical cord blood and adult peripheral blood

Growing interest surrounds adoptive cellular therapies utilizing Natural Killer (NK) cells, which can be obtained from various sources, including umbilical cord blood (UCB) and adult peripheral blood (APB). Understanding NK cell receptor expression and diversity in such cellular sources will guide future therapeutic designs. We used a 20-color flow cytometry panel to compare unstimulated and cytokine-activated UCB and APB NK cells. Our analysis showed that UCB NK cells express slightly higher levels of the immune checkpoints PD-1, TIGIT, and CD96 compared to their APB counterparts. Unsupervised hierarchical clustering and dimensionality reduction analyses revealed enrichment in CD56^neg as well as mature NKp46^neg and CD56⁺CD16⁺ NK cell populations in UCB whereas CD57⁺ terminally differentiated NK cells with variable expression of KIRs and CD16 were found in APB. These populations were conserved following stimulation with IL-12, IL-15, and IL-18. Cytokine stimulation was associated with the downregulation of TIGIT and CD16 on multiple NK cell subsets in UCB and APB. Among UCB CD16⁻ NK cell populations, TIGIT⁺ NK cells produced more IFN-γ than their TIGIT⁻ counterparts. Our data demonstrate higher immune checkpoint expression on UCB NK cells compared to APB. However, the expression of TIGIT immune checkpoint is not indicative of NK cell exhaustion.     

Major basic protein, but not eosinophil cationic protein or eosinophil protein X, is related to atopy in cystic fibrosis.

Increased eosinophil granule proteins have been described in serum and sputum samples of patients with cystic fibrosis (CF). It has been assumed that eosinophil degranulation is enhanced in atopic subjects - as in asthmatics. Since in CF no differences in eosinophil cationic protein (ECP), eosinophil protein X (EPX), and eosinophil peroxidase between atopic and nonatopic subjects have been detected, we investigated whether major basic protein (MBP) is increased in serum and sputum samples derived from atopic (n = 14) compared with nonatopic CF subjects (n = 26). In CF patients, high mean serum (sputum) levels of ECP 29.7 microg/l (2.7 mg/l), EPX 53.7 microg/l (7.9 mg/l), and MBP 984.6 microg/l but low sputum MBP levels (57.4 microg/l) were measured. In addition, in serum and in sputum samples, a significant correlation between MBP and ECP (P<0.03 and P<0.0001, respectively) or EPX (P<0.05 and P<0.0004, respectively) was detected. By subdivision of the patients into allergic and nonallergic subjects, significant differences were found for serum MBP values only(mean 1382.2 microg/l vs. 770.5 microg/l; P<0.0001), but not for ECP or EPX serum levels or for eosinophil proteins in sputum. Although no differences between atopic and nonatopic CF patients in ECP and EPX were found, serum MBP levels were higher in patients sensitized to inhalant allergens than in nonsensitized subjects. These results indicate differential release of eosinophil granule proteins in peripheral blood from eosinophils, and they also indicate that MBP in serum likely is to be a better discriminator of atopy in CF.     

多参数流式细胞术对外周血白血病免疫分型的研究

目的 :探讨多参数流式细胞术、CD45/SCC设门技术和三色荧光标记抗体 ,检测外周血在白血病免疫分型中的临床应用及其意义。方法 :对检测标本以CD45- Percp/SSC设门技术及流式细胞仪多参数分析技术 ,采用单克隆抗体三色标记对白血病患者的细胞群体进行免疫表型分析。结果 :195例白血病患者 ,其中急性白血病 14 4例 ,慢性白血病 51例。 14 4例急性白血病患者中 ,13 7例出现可供分析的白血病细胞独立群体。免疫分型结果ALL 66例 ,AML 67例 ,未能分型 4例。 2 7例AL表达 2个不同系列的免疫标记 (2 0 % )。分析了各类白血病的免疫表型的特征 ,AL共表达不同系列的抗原是一种常见现象。结论 :利用CD45 Percp/SSC设门技术及流式细胞仪多参数分析技术 ,可对白血病细胞群体进行准确的免疫表型检测和研究 ,有助于指导临床治疗及判断预后     

Pine resin and biopin ointment: effects of water-soluble fractions on cytokine production by peripheral blood neutrophils

We studied the effects of water-soluble fractions of pine resin and Biopin-10 and Biopin-20 ointments used for the therapy of burns, wounds, and purulent and inflammatory diseases on spontaneous and induced synthesis of tumor necrosis factor and interleukins 1, 2, and 8 by human peripheral blood neutrophils in vitro. These preparations contain various bioactive substances producing opposite and dose-dependent immunomodulatory effects. Our results indicate that the composition and doses of preparations should be selected to achieve the maximum therapeutic effect.     

应用四色荧光标记流式细胞术检测外周血淋巴细胞亚群的变化

目的 探讨四色荧光标记流式细胞术(Flow cytometry,FCM)检测鼻咽癌患者服用云芝丹参胶囊后外周血淋巴细胞亚群:辅助性T淋巴细胞(CD4 ),抑制性和细胞毒T淋巴细胞(CD8 ),B淋巴细胞(CD19 ),NK(CD16 CD56 ) 细胞的绝对数和百分率等的变化.方法 收集鼻咽癌患者27例,设立中药组和安慰剂对照组,采用四色荧光标记流式细胞术对服用云芝丹参胶囊后的鼻咽癌患者外周抗凝全血的淋巴细胞亚群CD4 细胞、CD8 细胞、B细胞、NK细胞进行绝对计数和相对计数,并对两组结果进行比较分析.结果 四色荧光标记流式细胞术结果显示:接受放射治疗的鼻咽癌患者在服用云芝丹参胶囊16周后,外周血T淋巴细胞的绝对数和百分率,以及Ts、Th细胞绝对数的下降均明显低于安慰剂组(P＜0.05);中药组和安慰剂组NK细胞百分率的变化均显著增高(P＜0.05); 但两组NK细胞绝对值的变化不存在明显差异(P＞0.05).结论 云芝丹参能明显减轻放射治疗对鼻咽癌患者的淋巴毒性.     

ABCB1 (P-glycoprotein) but not ABCC1 (MRP1) is downregulated in peripheral blood mononuclear cells of spontaneously hypertensive rats

Although the kidney is a major target in hypertension, several studies have correlated important immune alterations with the development of hypertension in spontaneously hypertensive rats (SHR), like increased secretion of pro-inflammatory cytokines, inflammatory infiltration in kidneys and thymic atrophy. Because adenosine-triphosphate-binding cassette sub-family B member 1 (ABCB1; P-glycoprotein) and adenosine-triphosphate-binding cassette sub-family C member 1 (ABCC1; multidrug resistance protein 1), two proteins first described in multidrug resistant tumors, physiologically transport several immune mediators and are required for the adequate functioning of the immune system, we aimed to measure the expression and activity of these proteins in peripheral blood mononuclear cells (PBMC), thymocytes, and also kidneys of normotensive Wistar Kyoto rats and SHR. Our results showed that ABCB1, but not ABCC1, activity was diminished (nearly 50%) in PBMC. Moreover, Abcb1b gene was downregulated in PBMC and kidney of SHR and this was not counterbalanced by an upregulation of its homolog Abcb1a, suggesting that the diminished activity is due to downregulation of the gene. No alteration was detected in ABCB1 activity in SHR thymocytes, indicating that this downregulation occurs after lymphocytes leave the primary lymphoid organs. Even though it is not known at present which parameter(s) is(are) responsible for this downregulation, it may contribute for the altered immune response observed in hypertension and to possible altered drug disposition in hypertensive individuals, resulting in greater drug interaction and increased drug toxicity. Raphael C. Valente and Márcia A. M. Capella contributed equally to this work.     

流式细胞术检测肿瘤患者外周血T淋巴细胞亚群研究

目的 探讨肿瘤患者T淋巴细胞亚群的变化及临床意义。方法 采用流式细胞术检测27例肿瘤患者和25例正常对照组的T淋巴细胞亚群。结果 肿瘤患者CD3^＋T细胞、CD4^＋T细胞和CD4^＋／CD8^＋比值明显低于对照组并有统计学意义，而CD8^＋T细胞显著高于对照组（P〈0．01）。结论 肿瘤患者的免疫功能下降。流式细胞术对肿瘤患者的免疫功能的检测具有快速、敏感、准确的特点，对于评价疗效、判断预后具有重要价值。     

Surface architectonics and ultrastructure of peripheral blood erythrocytes in tumor patients

Scanning and transmission electron microscopy revealed similar changes of erythrocyte surface and ultrastructure in patients with lung, stomach and colorectal cancer, head and neck tumors. The number of discocytes was sharply reduced, the percentage of transitional, prehemolytic, and degenerative forms increased, while erythrocyte ultrastructure was often disordered. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 6, pp. 680–682, June, 1999     

Signet Ring Cell Carcinoma of the Stomach: A Morphometric, Ultrastructural, and DNA Cytometric Study

The present study was undertaken to determine whether or not signet ring cell (diffuse, isolated cell) gastric carcinomas display a specific profile at the ultrastructural, morphometric, and DNA cytometric levels. Thirty-two cases of gastric carcinoma and 8 cases of peptic ulcer (control group) were studied with electron microscopy, morphometry, flow cytometry, and image cytometry. Despite the ultrastructural cellular heterogeneity of signet ring cell carcinomas, the neoplastic cells display fairly constant morphometric features: The cellular and nuclear volumes are significantly smaller than those of the other types of gastric carcinomas and closely resemble those of normal foveolar cells. The relatively small size of signet ring cell carcinoma nuclei fits with the high percentage of the cases of this type of gastric carcinoma that are either diploid or nearly diploid. There is a relationship between the infiltrative pattern of growth of gastric carcinoma (regardless of histologic subtype and ultrastructural cell differentiation) and the small size of neoplastic cells and their nuclei.     

Salbutamol pretreatment does not change eosinophil percentage and eosinophilic cationic protein concentration in hypertonic saline-induced sputum in asthmatic subjects

BACKGROUND: Sputum induction by inhalation of hypertonic saline (HS) is usually preceded by beta2-agonist pretreatment, to prevent severe bronchoconstriction. OBJECTIVE: To evaluate whether salbutamol pretreatment may influence cell counts and concentrations of soluble mediators in induced sputum. METHODS: We studied 22 patients who randomly underwent HS sputum induction after pretreatment with either 200 microg salbutamol or placebo. Sputum was induced by means of HS inhalation (3, 4, 5% NaCl, 10 min each), measuring FEV1 every 5 min until it fell >/= 20% from baseline. Collected sputum was diluted 1 : 1 with 0.1% DTT, incubated at 37 degrees C for 20 min, and total and differential cell counts were measured. ECP and histamine levels were measured in the supernatant. RESULTS: Sputum volume, percentages of inflammatory cells, squamous cell counts and quality of the slides were not different after the two pretreatments, while sputum total inflammatory cells after salbutamol tended to be higher than after placebo (8.3 [1-41] 10(6) vs 6.3[0.2-40] x10(6); P = 0.09). Eosinophilic cationic protein (ECP) did not significantly change (260 [8-900] microg/L after salbutamol vs 200 [8-800] microg/L, n = 19), while histamine levels tended to be lower after salbutamol (140.9 [39.9-236.5] nm) than after placebo (190.4 [72. 2-322.6] nm, P = 0.09, n = 17). The airway response to HS inhalation was significantly greater after placebo and the duration of the test was significantly different (median: 15 min after placebo and 30 min after salbutamol). Similar results were obtained when patients who differed for more than 15 min in the duration of HS-inhalation in the two tests were selected (n = 11). CONCLUSION: Salbutamol pretreatment reduces the severity of bronchoconstriction induced by HS inhalation without significantly affecting the percentages of inflammatory cells and the levels of soluble mediators in induced sputum.     

Curcumin increases gelatinase activity in human neutrophils by a p38 mitogen-activated protein kinase (MAPK)-independent mechanism

Abstract

Curcumin has been found to possess anti-inflammatory activities and neutrophils, key players in inflammation, were previously found to be important targets to curcumin in a few studies. For example, curcumin was found to induce apoptosis in neutrophils by a p38 mitogen-activated protein kinase (MAPK)-dependent mechanism. However, the role of curcumin on the biology of neutrophils is still poorly defined. To study the role of curcumin on neutrophil degranulation and to determine the role of p38 MAPK, human neutrophils were freshly isolated from healthy individuals and incubated in vitro with curcumin. Degranulation was studied at three levels: surface expression of granule markers by flow cytometry; release of matrix metallopeptidase-9 (MMP-9 or gelatinase B) enzyme into supernatants by Western blot; and gelatinase B activity by zymography. Activation of p38 MAPK was studied by monitoring its tyrosine phosphorylation levels by western blot and its role by the utilization of a pharmacological inhibitor. The results indicate that curcumin increased the cell surface expression of CD35 (secretory vesicle), CD63 (azurophilic granules), and CD66b (gelatinase granules) in neutrophils. Also, curcumin increased the release and enzymatic activity of gelatinase B in the extracellular milieu and activated p38 MAP kinase in these cells. However, in contrast to fMLP, curcumin-induced enzymatic activity and secretion of gelatinase B were not reversed by use of a p38 inhibitor. Finally, it was found that curcumin was able to enhance phagocytosis. Taken together, the results here demonstrate that curcumin induced degranulation in human neutrophils and that the increased gelatinase activity is not dependent on p38 MAPK activation. Therefore, degranulation is another human neutrophil function that could be modulated by curcumin, as well as phagocytosis.