Identification of an eosinophil chemotactic factor from anopheline mosquitoes as a chitinase family protein.

Anopheline mosquitoes play an essential role in malaria transmission. The mosquito salivates copiously when probing for the location of a blood vessel. We found that the saliva of anopheline mosquitoes has chemotactic activity for naive eosinophils or neutrophils. The major eosinophil chemotactic component in saliva was shown to be one of the chitinase family proteins. A similar chitinase family protein was found also in the midgut of the anopheline mosquito. Production of antibodies to the chitinase family protein was generally observed in the sera of residents of a malaria endemic area. Both Plasmodium falciparum-infected and uninfected individuals had antibodies to chitinases. These results suggest that the chitinase family protein in mosquito saliva contributes to eliciting an inflammatory response of eosinophils in the host skin followed by antibody production in the host.

Association of plasma eotaxin levels with the presence and extent of angiographic coronary artery disease.

Eotaxin (CCL11) is an eosinophil-specific chemoattractant which has been found to be highly expressed at sites of vascular pathology. In the present study, we aimed to evaluate the association of plasma eotaxin levels with the presence and extent of angiographic coronary artery disease (CAD). Three hundred and fifty six consecutive patients attending for elective coronary angiography were investigated. Compared with 111 patients without CAD, 245 with CAD showed higher eotaxin concentrations [median (interquartile range): 76.0 (56.3-103.0)pg/ml versus 116.0 (80.5-162.0)pg/ml, respectively; P<0.001]. Importantly, a significant Spearman correlation was found between eotaxin levels and the extent score of coronary artery stenosis (r=0.449, P<0.001). A stepwise increase in plasma levels of eotaxin was also found depending on the number of >50% coronary stenosis: median value 76.0 pg/ml in CAD(-) subjects, 96.0 pg/ml in 1-vessel disease, 128.0 pg/ml in 2-vessel disease, and 129.0 pg/ml in 3-vessel disease (P<0.001 for trend). After confounding variables were controlled for, multiple stepwise regression analysis demonstrated that plasma eotaxin was an independent predictor of angiographic extent of CAD (beta=0.426, P<0.001). Our data suggest that increased eotaxin levels are associated with the presence of CAD and that circulating levels of this chemokine may reflect the extent of coronary atherosclerosis.

Circulating levels of MCP-1 and eotaxin are not associated with presence of atherosclerosis or previous myocardial infarction.

The chemokines are a family of signalling proteins that participate in regulation of the immune system and have been implicated in the pathogenesis of vascular diseases. Deleting the gene encoding the chemokine MCP-1 in mouse models of atherosclerosis reduces lipid lesion formation and circulating chemokines are upregulated in man immediately following myocardial infarction (MI) or coronary angioplasty. We have therefore investigated whether circulating levels of two chemokines (MCP-1 and eotaxin) differ between subjects with and without atherosclerosis. We have used three different methods of measuring the presence and extent of atherosclerosis in human subjects: duplex ultrasonography of the carotid arteries and clinical diagnosis of coronary heart disease on individuals from the general population and coronary angiography on patients with suspected heart disease. There was no difference in the levels of circulating MCP-1 or eotaxin, measured by ELISA, between subjects with and without atherosclerosis. Furthermore, any increase in circulating MCP-1 following acute MI must be short-lived, since chemokine levels were not different in subjects who had had an MI previously compared to those who had not. We conclude that although there may be a transient increase in circulating chemokine levels following coronary angioplasty, there is no difference in the levels of circulating MCP-1 or eotaxin in subjects with and without atherosclerosis.

Influence of age and gender on serum eotaxin concentration in healthy and allergic people.

BACKGROUND: Eotaxin is one of the important chemokines that modulate allergic inflammation. In many studies a correlation between an elevated serum concentration of eotaxin, allergen exposure and allergic symptoms has been confirmed. Influence of other factors on eotaxin concentration is feebly recognized. We made an attempt to assess the influence of age and gender on the serum eotaxin level in healthy people and in patients with intermittent IgE-mediated rhinoconjunctivitis (AR). METHODS: The serum eotaxin level was measured in 245 healthy people and 241 patients with AR before the pollen season with the ELISA technique (KITS, R&D USA, pg/ml). The parametric tests and linear regression analysis were used in statistical calculations. RESULTS: There were no differences between the allergic group and the healthy one in the mean age (accordingly: 31.3 +/- 11.6 yrs. vs. 31.6 +/- 12.5 yrs.; p=0.1) and the mean serum eotaxin content (118.1 +/- 44.9 pg/ml vs. 116.3 +/- 34.8 pg/ml; p=0.3). A significant relationship between the serum eotaxin level, gender and age was revealed in both groups and regression models were derived. A linear correlation between age (semi-partial correlation beta = 0.47, p = 0.0000001) and gender (semi-partial correlation beta = 0.3, p = 0.0000001), on the one side, and the serum eotaxin level, on the other, was found for the allergic people. In the control group a similar relationship between the serum eotaxin level and age (semi-partial correlation coefficient beta = 0.63, p = 0.0000001) and gender (semi-partial correlation factor beta = 0.23, p = 0.000006) was observed. CONCLUSIONS: Age and sex significantly influence the serum eotaxin content in healthy people and patients with IgE-mediated rhinoconjunctivitis.

Activation of humoral immunity and eosinophils in neuromyelitis optica.

OBJECTIVE: To study immunologic alterations in patients with neuromyelitis optica (NMO). METHODS: The authors studied 8 patients with NMO together with 16 healthy subjects, 16 patients with relapsing remitting multiple sclerosis (RRMS), and 16 patients with secondary progressive MS (SPMS), matched for age and sex, as controls. Because recent histopathologic studies have demonstrated that active NMO lesions consist of perivascular immunoglobulin (Ig) deposition and eosinophil infiltration, IL-5, IL-6, IL-12, IgG, and IgM production by anti-myelin oligodendrocyte glycoprotein (MOG) mononuclear cells in peripheral blood and CSF were selected for study using ELISPOT. Eotaxin-2 (Eo-2) and eotaxin-3 (Eo-3) levels were also assessed using ELISA and eosinophil cationic protein (ECP) levels by radioimmunoassay. RESULTS: MOG-specific responses in CSF showed significant increase in IL-5, IL-6, IgG, and IgM secreting cells in NMO patients compared with patients with RRMS, SPMS and healthy subjects. Interestingly, numbers of IgM secreting cells were significantly higher than identical specificity IgG secreting ones. Moreover, CSF Eo-2, Eo-3, and ECP levels were also significantly higher in NMO patients compared to all three control populations. Anti-MOG IL-12 secreting cells were increased in CSF and peripheral blood from NMO, RRMS, and SPMS patients when compared to healthy subjects. CONCLUSIONS: These observations suggest that neuromyelitis optica is associated with a major humoral immune response (particularly anti-MOG IgM production) and eosinophil activation present exclusively in CSF.

Effect of influenza vaccinations on immune response and serum eotaxin level in patients with allergic bronchial asthma.

BACKGROUND: One of the most promising markers of allergic inflammation is eotaxin, which has a selective influence on the migration of eosinophils. Its serum content significantly correlates with the intensity of allergic symptoms, so it might be interesting to know whether vaccination has any influence on serum expression of this chemokine. AIMS: Comparison of the humoral response to influenza vaccine and post-vaccination changes in the serum eotaxin level in patients with allergic bronchial asthma and healthy controls. METHODS: Forty-two asthmatics and 45 healthy individuals were vaccinated with a single dose of influenza subunit vaccine (Influvac). The serum eotaxin level and the antibody response to haemagglutinin (HI) and neuraminidase (NI) glycoproteins were measured before and after vaccination. RESULTS: A significant increase of geometric mean titres of HI and NI was observed in both groups. There were no significant differences between the groups in meanfold increase of HI and NI titres, response rate and protective level of HI. After vaccination, a significant decrease of the mean serum eotaxin value was observed in patients with asthma (149.4 +/- 71.0 versus 125.1 +/- 67.0, p= 0.0017), while no similar effect was present in healthy individuals (153.4 +/- 56.9 versus 159.3 +/- 54.4, p= 0.5). CONCLUSIONS: The results indicate that in patients with allergic bronchial asthma influenza vaccinations assure efficient protective antibody level and modulate the serum level of eotaxin.

Circulating interleukin 16 (IL-16) in children with atopic/eczema dermatitis syndrome (AEDS): a novel serological marker of disease activity.

BACKGROUND: Chemokines play a central role in atopic eczema/dermatitis syndrome (AEDS). Interleukin 16 (IL-16) has been described as a main cytokine involved in CD4+ cell recruitment during inflammation. Recently the influx of CD4+ lymphocytes has been related to the up-regulation of IL-16 in AEDS skin lesions. Circulating beta-chemokines (Eotaxin and RANTES) and IL-16 were investigated in children with AEDS to correlate their presence with the severity of the disease. We also measured serum levels of soluble CD30 (sCD30), a marker of Th2 immune responses related to AEDS disease activity. METHODS: Serum levels of eotaxin, RANTES, IL-16 and sCD30 were measured by immunoenzymatic assay in paediatric patients with pure AEDS (pAEDS, n = 39); the severity of the disease was graded by SCORAD. Fifteen children with AEDS in presence of respiratory allergy (AEDS+A), 15 with allergic asthma (A) and 20 age-matched healthy donors were investigated as control groups. RESULTS: When compared to normals, high amounts of Eotaxin and IL-16 were detected in sera of pAEDS (P = 0.002; P < 0.0001), AEDS+A (P = 0.02; P = 0.01) and A patients (P = 0.004; P = 0.03) with respect to normals. Serum levels of RANTES were also elevated in pAEDS patients, significantly higher than normals (P = 0.009), whereas no statistically significant differences could be detected between pAEDS and AEDS+A or A groups. IL-16 was progressively increased in the different stages of pAEDS, with a positive correlation between IL-16 and both SCORAD and sCD30 (P < 0.0001). CONCLUSION: We suggest that IL-16 could serve as a useful marker of disease activity in childhood pAEDS.

Effects of an eosinophil chemotaxis inhibitor, TAK-661, on antigen-induced asthmatic responses in allergic sheep.

Eosinophils have been shown to play a role in allergen-induced airway responses. The aim in this study was to examine the effects of TAK-661, a newly developed product as a specific inhibitory agent of eosinophil chemotaxis, on antigen-induced asthmatic responses in allergic sheep model. Seven Ascaris-sensitive, "dual-respondent" allergic sheep were provocated by an Ascaris suum antigen or phosphate-buffered saline 2 hrs after intra-stomach administration of TAK-661 or a placebo. Pulmonary resistances were measured throughout the experiment, and airway responsiveness to methacholine, bronchoalveolar lavage (BAL), and histological examination were performed 8 hrs after the antigen challenge. Antigen provocation induced dual-phase bronchoconstriction, eosinophilia in BAL and eosinophil infiltration into the airway wall, and an increase in airway responsiveness in placebo-treated sheep. The administration of TAK-661 significantly reduced the bronchoconstriction during the late phase, along with the inhibition of eosinophilia in BAL and the eosinophil infiltration into the airway wall. TAK-661 had a tendency to reduce early-phase bronchoconstriction and airway hyperresponsiveness, but there were no significant differences. These findings suggest that the eosinophil accumulation into the airway induced by antigen provocation may contribute to the development of late-phase bronchoconstriction, however, the development of airway hyperresponsiveness during late asthmatic response may not always be due to only eosinophilic inflammation in the airway.

Increased release of matrix metalloproteinase-9 in the plasma of acute severe asthmatic patients.

BACKGROUND: Matrix metalloproteinases (MMPs) are likely to be relevant mediators of the extracellular matrix (ECM) degradation and airway remodelling. OBJECTIVE: We have compared the levels of MMPs, eotaxin and soluble interleukin 2 receptor (IL-2R) in the plasma of healthy subjects, atopic patients and asthmatic patients. METHODS: The asthmatic patients were separated into two groups, either well controlled on inhaled therapy or acute severe asthma. Patients with acute severe disease had all received systemic corticosteroids from 12 to 48 h before the blood was taken. Blood was recovered in EDTA tubes, incubated with either f MLP, PMA or vehicle for 10 min and centrifuged. MMP-9, TIMP-1, IL-2R and eotaxin levels were measured in the plasma by ELISA. Moreover, the activity of MMPs was also evaluated by zymography. RESULTS: An increased basal level of MMP-9 and IL2-R was observed in acute severe asthma. Following stimulation with f MLP and PMA there was an enhanced production of MMP-9 in the plasma of all groups of patients. However, the MMP-9 level was significantly enhanced in acute severe asthma, compared with the others. No difference was found for the TIMP-1 level between the patients. The eotaxin level in plasma was found to be significantly lower in acute severe asthmatics compared with the others groups. Zymography technique showed a significant increased activity of MMP-9 (92 kDa) but not MMP-2 (66 kDa) in the plasma of patients with acute asthma. CONCLUSION: The increased in MMP-9 production and activity observed in the present study suggests a process of extracellular matrix degradation in acute severe asthmatic patients and proposes MMP-9 as a non-invasive systemic marker of inflammation and airway remodelling in asthma.

Increased plasma eotaxin in atopic dermatitis and acute urticaria in infants and children.

BACKGROUND: The previously reported eotaxin overexpression in the lesional skin of atopic dermatitis (AD) led us to the assumption that circulating levels of eotaxin may be elevated too. We sought to investigate the plasma expression of eotaxin in children with skin allergy in relation to clinical activity and type of lesions. METHODS: Plasma eotaxin was assayed in 78 infants and children, of whom 16 had AD, 19 had acute urticaria (AU), and 43 were healthy matched subjects. Seven children in the group of AU were resampled for plasma eotaxin after clinical remission. RESULTS: The plasma eotaxin levels in AD (median=158 pg/ml, mean [SD]=168 [61] pg/ml) were significantly higher than the control values (median=60 pg/ml, mean [SD]=59.5 [18.5] pg/ml). Not only did patients with AU demonstrate elevated plasma eotaxin levels (median=126 pg/ml, mean [SD]=124 [33] pg/ml), but also a significant decline occurred on follow-up. The coexistence of angioedema with AU did not cause any further increase in plasma eotaxin expression. Plasma eotaxin levels were significantly higher in AD than in AU, probably reflecting the chronic nature of eczematous AD lesions. The plasma eotaxin levels did not correlate with serum total IgE, peripheral blood absolute eosinophil count, or age of the patients. However, there was a positive correlation between age and plasma eotaxin in the control group. CONCLUSION: Our findings imply that circulating levels of eotaxin increase in AD and during flares of AU, probably to serve in the recruitment and activation of eosinophils. It may also represent a biomarker of lesional activity.

Chemokines in patients with ischaemic heart disease and the effect of coronary angioplasty.

Percutaneous coronary transluminal angioplasty (PTCA) may release inflammatory mediators such as chemokines. Monocyte chemoattractant protein-1 (MCP-1) and eotaxin (EOX) are monocyte- and eosinophil-specific chemokines involved in the inflammation and pathogenesis of coronary atherosclerosis. A total of 28 patients undergoing elective PTCA, 20 coronary artery disease (CAD) patients undergoing coronary angiography and 28 healthy controls were studied. In PTCA patients before the procedure, MCP-1 plasma levels (441+/-64 pg/ml) were similar to those of CAD patients (430+/-24 pg/ml), and significantly higher compared with controls (145+/-17 pg/ml, P<0.01). MCP-1 rose significantly after 3 and 6 months following PTCA (696+/-89 and 876+/-86 pg/ml, respectively, P<0.01 vs. before PTCA). EOX plasma levels (155+/-14 pg/ml) were similar to those of CAD patients (157+/-14 pg/ml), but significantly higher compared with controls (83.2+/-10 pg/ml, P<0.05). EOX rose significantly 24 h (273+/-41 pg/ml, P<0.05) but not 3 months after PTCA (160+/-20 and 158+/-19 pg/ml, respectively). These findings indicate that chemokine-induced monocyte- and eosinophil-specific chemoattraction is stimulated in patients with coronary artery disease. MCP-1 levels remain significantly elevated for at least 6 months following elective PTCA, suggesting an inflammatory stimulation.

[Serum levels of NO products, IL-8, RANTES and eotaxin in infantile patients with atopic dermatitis].

Inflammatory mechanisms play an important role in the pathogenesis and the expansion of the skin lesion in AD. The serum levels of NO product, IL-8, RANTES and eotaxin, which are considered to an index of the inflammatory response, were measured in infants diagnosed as AD. The serum levels of NO product, RANTES and eotaxin were higher in the infantile AD patients with the systemic skin lesion compared with controls. The higher levels of NO product were shown with the expansion of the skin lesion. In AD patients, the serum levels of NO product were significantly correlated with the serum levels of eotaxin (r = 0.615, p < 0.001). These results suggest that NO product bears an important function in the allergic inflammation, which is concerned with the lesion expansion of the infantile AD patients and may be an index of the allergic inflammation.

[Blood serum eotaxin and eosinophil cationic protein in asthmatic patients]. / Stezenia eotaksyny i eozynofilowego bialka kationowego w surowicy chorych na astme oskrzelowa.

Eotaxin belongs to CC class of chemokines and is a potent eosinophil chamoattractant. Activated eosinophils are able to release many cytotoxic proteins, including eosinophil cationic protein (ECP), which has central role in allergic inflammation. The aim of this study was to assess eotaxin and ECP levels in plasma of atopic asthma patients in stable period of the disease. 19 patients with asthma and 10 healthy controls took part in this study. ELISA test was used to measure eotaxin (kits from R&D, pg/ml) and ECP (kits from Pharmacia, mg/l) levels. Plasma eotaxin level (mean +/- SD) was 176.52 +/- 50.3 (range 89-288) in asthma patients and 101.42 +/- 49.4 (range 35-206) in control group (p < 0.001). Plasma ECP concentration was 16.7 +/- 6.4 (6.3-28) and 16.8 +/- 17.1 (3.1-61.6), respectively (n.s). There was correlation between plasma eotaxin and ECP levels (Pearsons correlation co. r = +0.5, p < 0.05) and between eotaxin and FEV1 (Pearsons correlation co r = -0.4, p < 0.05) in asthma patients. We suggest that measurement of eotaxin and ECP levels as well may be useful indicator of disease.

Eotaxin and impaired lung function in asthma.

We performed an association study of plasma eotaxin levels, eosinophil counts, total IgE levels, asthma diagnosis, and lung function in an ethnically diverse and geographically dispersed population. We studied 515 asthmatic and 519 normal subjects, none of whom was taking inhaled or oral corticosteroids. Logistic regression analysis demonstrated a direct relationship between asthma diagnosis and eotaxin levels (p < 0.0001). The odds of an asthma diagnosis increased with eotaxin quartile, with the highest quartile having an odds ratio of 5.4 (95% CI 3.2 to 9.2, p < 0.001) compared with the lowest eotaxin quartile. Eotaxin levels were inversely related to lung function (p < 0.001), with the mean percent predicted FEV(1) in the highest eotaxin quartile being 13.5 percentage points (SEM 2.1, p < 0.001) less than that in the lowest quartile. Plasma eotaxin levels were associated with asthma and inversely related to lung function independent of age, race, sex, or smoking status. When combined with eosinophil counts and IgE levels, eotaxin levels contributed to the odds of an asthma diagnosis and of impaired lung function. Our results are the first to associate eotaxin levels with asthma diagnosis and compromised lung function in a large geographically and ethnically diverse population.

Elevated plasma eotaxin levels in patients with acute asthma.

BACKGROUND: The eosinophil chemotactic and activating effects of eotaxin and the known association of eosinophils with asthma suggest that eotaxin expression is increased during asthma exacerbations. OBJECTIVE: We sought to determine whether plasma eotaxin levels are elevated in patients presenting for emergency treatment of acute asthma and to correlate eotaxin levels with disease activity and responses to treatment. METHODS: A case-control study of plasma eotaxin levels was performed in the 46 patients who presented for emergency asthma treatment and 133 age-, sex-, and ethnicity-matched subjects with stable asthma. RESULTS: Plasma eotaxin levels were significantly higher in 46 patients with acute asthma symptoms and airflow obstruction (520 pg/mL [250, 1100 pg/mL]; geometric mean [-1 SD, +1 SD]) than in 133 subjects with stable asthma (350 pg/mL [190, 620 pg/mL]; P =.0008). Among the patients with emergency asthma flares, those who responded to asthma treatment with an increase in peak expiratory flow rate by an amount equal to at least 20% of their predicted normal value had lower eotaxin levels than those who did not (410 pg/mL [210, 800 pg/mL] and 660 pg/mL [300, 1480 pg/mL], respectively; P =.04). CONCLUSION: These findings imply that eotaxin either is mechanistically involved in acute asthma or serves as a biomarker for activity of the CCR3 receptor ligand system, which is functionally linked to asthma.

Development of a sensitive enzyme-linked immunosorbent assay for eotaxin and measurement of its levels in human blood.

The CC chemokine eotaxin is potent eosinophil-selective chemoattractant, and it is thought that the function of eotaxin is closely related to the recruitment of eosinophils in certain inflammatory reactions. In order to learn more about the biological role of this molecule, we have developed a new sandwich ELISA method to measure human eotaxin using two monoclonal anitibodies and purified recombinant eotaxin as a standard. The minimal detectable concentration of eotaxin in this assay was 1.5 pg/ml, and the working range was 3.1--200 pg/ml with low CVs (< 10%). Both within- and between-run precision levels were less than 6.7% of the CVs. The dilution curves of two serum and two spiked plasma samples showed good linearity and the recovery range was 92.8--103.3%. No cross-reactivity was found with other similar chemokines. MCP-1, MCP-2, MCP-3, MCP-4, eotaxin-2 and RANTES. This assay was sensitive enough to measure the circulating eotaxin levels of healthy volunteers. However, the eotaxin levels in serum samples (mean+/-SD; 68.6+/-13.4 pg/ml, n=15) were significantly higher than those in matched plasma samples (19.2+/-5.4 pg/ml) separated from blood collected in tubes containing EDTA. Kinetic studies revealed that the eotaxin levels in serum markedly increased depending on the elapsed time before separation from blood cells, but such changes in EDTA-plasma were negligible up to 4 h at 25 degrees C. Our new ELISA is an accurate and useful method for quantifying human eotaxin in blood and demonstrates that the process of preparing blood samples affects the measurement of the eotaxin levels.

Kinetic study of eosinophil chemotactic factor production with reference to eosinophilia and granuloma formation in mice infected with Schistosoma japonicum.

Kinetic changes of eosinophil chemotactic factor (ECF) production from granulomas, splenic T-cells or mast cells were examined with reference to granuloma formation around newly deposited single eggs in Schistosoma japonicum-infected mice. The peri-ovular granulomas began to appear at around 5 weeks post-infection (p.i.). Their size reached a peak at 6 weeks and then decreased gradually. Up to 8 weeks p.i., eosinophils were the predominant cell type in the granulomas. ECF-release from isolated granulomas paralleled the size of granulomas. Circulating ECF-A, which was assumed to be derived from mast cells, was also detected 6 weeks afterwards in parallel with the level of specific IgE antibody level against egg antigens in the serum. The circulating ECF-A peaked at 8 weeks and decreased after 10 weeks. Spleen cells began to produce ECF specific to bone-marrow eosinophils began at 5 weeks p.i., reached a peak at 6 weeks and then decreased rapidly. On the other hand, the production of ECF specific to eosinophils obtained from the peritoneal cavity began at 6 weeks and decreased rapidly thereafter. These results suggest that various kinds of host-derived ECFs seem to contribute, in one way or an other, to the accumulation of eosinophils in and around granulomatous lesions. The possible role of these ECFs in eosinophil mobilization from the site of production to the inflamed site is discussed.

GM-CSF and eosinophil chemotactic factors in an acute lymphoblastic leukemia patient with eosinophilia.

We describe a patient with common acute lymphoblastic leukemia associated with blood and cerebrospinal fluid (CSF) eosinophilia. Serum obtained at onset and conditioned medium prepared from T cells obtained at remission stimulated with interleukin-2 contained eosinophil colony stimulating activity (Eo-CSA), which was confirmed to be predominantly GM-CSF. Leukemic cell conditioned medium and serum obtained at remission contained no Eo-CSA. The CSF contained increased eosinophil chemotactic activity, however, this factor was not identified.

The formation of eosinophil and neutrophil chemotactic activity during a pollen season and after allergen challenge.

Heat-stable (HS) and heat-labile (HL) neutrophil chemotactic activities (NCAs) have been demonstrated in serum after allergen challenge of subjects with asthma. In this investigation, we have studied the possible occurrence of similar activities in 20 atopic individuals on natural exposure to allergen, that is, during the birch-pollen season. Since eosinophil accumulation is a hallmark of an ongoing allergic inflammation in the respiratory tract also, the possible production of eosinophil chemotactic activity (ECA) was examined in serum after allergen challenge and at natural exposure to pollen. Both HL-NCA and HL-ECA were produced to a significant extent (p less than 0.001) during the season, with the peak of activities occurring simultaneously with the peak pollen count. HL-ECA was produced after allergen challenge of subjects with asthma in the laboratory, as has been demonstrated for NCA previously. The activity of the HS-NCA was unaltered during season. Gel-filtration studies of the major HL-NCA and HL-ECA indicated a molecular weight for both activities of 100 to 150,000, and the activities produced during season cochromatographed with the HL-NCA and HL-ECA produced after allergen challenge in the laboratory, suggesting that all these activities are due to one and the same molecule. The results suggest that the heat-labile chemotactic activity found in serum of atopic subjects and subjects with asthma after allergen exposure may be involved in the attraction of eosinophils and neutrophils to the site of allergic inflammation.

Serum levels of neutrophil and eosinophil chemotactic activities in mastocytosis.

Neutrophil and eosinophil chemotactic activities (NCA and ECA) were measured in serum from twenty-two patients with urticaria pigmentosa or systemic mastocytosis. NCA was also measured after heating serum to 56 degrees C (heat-stable NCA). Although these factors were increased in about half of the patients there was no correlation with histamine release as estimated by the excretion of the main histamine metabolite methylimidazoleacetic acid (MelmAA) in urine. A significant increase in heat-stable NCA, however, was found in patients with pruritus and abnormal high values of MelmAA. It is concluded that only heat-stable NCA is a specific mast cell mediator, but that the heat-labile NCA and ECA are dependent on mast cells for their production by a different cell, tentatively identified as the macrophage.