Massive Eosinophilic Infiltration Research Articles

Churg-Strauss syndrome.

A syndrome comprising asthma, allergic rhinitis, pulmonary and systemic small-vessel vasculitis, and extravascular granulomas was described in 1951 by Churg & Strauss, mainly from autopsied cases (1). Clinical studies of patients with polyarteritis nodosa, associated asthma, pulmonary in®ltrates, and eosinophilia had been reported previously (2±5). Churg & Strauss described the pathologic lesions and distinguished this entity from polyarteritis nodosa. They described basic anatomic changes consisting of ``widespread vascular lesions of the type seen in polyarteritis nodosa, and of characteristic tissue alteration in the vessel wall and in the extravascular system. This tissue alteration . . . comprised necrosis of eosinophilic exudate, severe `®brinoid' collagen change, and granulomatous proliferation of epithelioid and giant cells.'' Churg & Strauss considered it to be a distinct histopathologic entity which they termed ``allergic granuloma''.

Effects of Th2 Cytokines on Chemokine Expression in the Lung: IL-13 Potently Induces Eotaxin Expression by Airway Epithelial Cells

Airway inflammation associated with asthma is characterized by massive infiltration of eosinophils, mediated in part by specific chemoattractant factors produced in the lung. Allergen-specific Th2 cells appear to play a central role in asthma; for example, adoptively transferred Th2 cells induced lung eosinophilia associated with induction of specific chemokines. Interestingly, Th2 supernatant alone administered intranasally to naive mice induced eotaxin, RANTES, monocyte-chemotactic protein-1, and KC expression along with lung eosinophilia. We tested the major cytokines individually and found that IL-4 and IL-5 induced higher levels of macrophage-inflammatory protein-1alpha and KC; IL-4 also increased the production of monocyte-chemotactic protein-1; IL-13 and IL-4 induced eotaxin. IL-13 was by far the most potent inducer of eotaxin; indeed, a neutralizing anti-IL-13 Ab removed most of the eotaxin-inducing activity from Th2 supernatants, although it did not entirely block the recruitment of eosinophils. While TNF-alpha did not stimulate eotaxin production by itself, it markedly augmented eotaxin induction by IL-13. IL-13 was able to induce eotaxin in the lung of JAK3-deficient mice, suggesting that JAK3 is not required for IL-13 signaling in airway epithelial cells; however, eosinophilia was not induced in this situation, suggesting that JAK3 transduces other IL-13-mediated mechanisms critical for eosinophil recruitment. Our study suggests that IL-13 is an important mediator in the pathogenesis of asthma and therefore a potential target for asthma therapy.

A third-phase cutaneous (very late phase) response after elicitation with dinitrofluorobenzene in passively or actively sensitized mice

Previous studies have reported that the mice passively sensitized with anti-dinitrophenol (DNP) IgE antibody exhibited IgE-mediated cutaneous reaction with an immediate phase response (IPR) at 1 h and a late phase response (LPR) at 24 h after the challenge of dinitrofluorobenzene (DNFB). We found that the third-phase inflammatory reaction with intense and persisting infiltration of eosinophils, named ‘very late phase reaction (vLPR)’, was induced following IPR and LPR in response to DNFB in actively and passively sensitized mice, and that the peak response of vLPR was at 8 days after the challenge. This reaction was slightly observed in non-sensitized mice. Since the accumulation of eosinophils in vLPR was markedly observed when compared with that of LPR at 24 h, the vLPR may be an important reaction in allergic diseases. The development of vLPR was partly decreased in mast cell-deficient WBB6F1-W/Wv mice and was absent in T cell-deficient BALB/c-nu/nu mice in passive sensitization. These results indicate that the vLPR in the triphasic cutaneous reaction may be mainly mediated by T cells and partially by mast cells and/or IgE antibody, and consequently lead to an intense ear swelling accompanying massive infiltration of eosinophils.

Th2-Induced Eotaxin Expression and Eosinophilia Coexist with Th1 Responses at the Effector Stage of Lung Inflammation

The T cell-mediated lung inflammation that is associated with allergic asthma is characterized mainly by massive eosinophil infiltration, which induces airway injury and the subsequent late-phase reactivity. Because Th2 cells are often isolated from asthmatic subjects, these cells are postulated to play a role in asthma pathogenesis. We report that adoptively transferred, influenza hemagglutinin-specific Th1 and Th2 cells induced different patterns of chemokines leading to different types of cellular infiltration. Th2 cells were sufficient to induce dramatic Ag-dependent lung eosinophilia and eotaxin expression; by contrast, Th1 transfer primarily induced neutrophil recruitment with little eotaxin production. To determine whether Th1 cells show inhibitory effects on Th2 cell-mediated responses, Th1 and Th2 cells were cotransferred. Hemagglutinin-specific Th1 cells did not inhibit Ag-induced lung eosinophilia, nor did they inhibit eotaxin expression. Furthermore, influenza virus infection of the lung in mice receiving hemagglutinin-specific Th2 cells also induced eotaxin expression and eosinophilia that could not be inhibited by the cotransfer of Th1 cells. Our results show that Th2-mediated allergic lung inflammation coexists with the Th1-mediated responses that are stimulated by diverse forms of Ags.

Kimura’s disease: an unusual cause of cervical tumour

An 11 year old Chinese boy developed a unilateral cervical mass associated with pronounced eosinophilia and a marked increase in IgE concentrations. A biopsy sample showed massive eosinophilic tissue infiltration...

A novel murine model of late‐phase reaction of immediate hypersensitivity

We describe here a novel experimental model of late-phase reaction of immediate hypersensitivity developed in mice. It consists of introducing small fragments of heat-coagulated hen egg white into the subcutaneous tissue of mice. After 14 days, animals challenged with purified ovalbumin into the footpad presented an immediate swelling of the paw peaking at 30 min, followed by two peaks of swelling at 6 and 24 h. Histological examination of the paws showed a massive eosinophil infiltration (more than 800 cells/5 microscopic fields). This intense infiltration persisted for more than 14 days after the challenge. Furthermore, in mice immunized with coagulated egg white the delayed swelling of the paws and eosinophilic infiltration were significantly higher than in mice immunized with the classical protocol of ovalbumin in alumen adjuvant. Transfer of lymph node cells obtained from mice implanted with heat-coagulated hen egg white induced footpad swelling and eosinophil infiltration in response to ovalbumin. High levels of ovalbuminspecific IgG1 but not of IgE were detected in the serum of these animals. The advantages of this model for the experimental study of late-phase reaction per se and its relevance to the study of allergic diseases such as asthma are discussed.

Dissociation in the control of cervical eosinophilic infiltration and collagenolysis at the end of pregnancy or after pseudopregnancy in ovariectomized steroid-treated rats.

Previous studies have demonstrated that during parturition the physiological ripening that permits dilation of the cervical canal is due to a widespread collagenolysis that follows a heavy polymorphonuclear leukocyte invasion of the uterine cervix. The aim of this study was to investigate whether there is any association between the ovarian steroid hormones involved in rat parturition and this phenomenon. Pregnant or pseudopregnant rats were ovariectomized (OVX) at Day 9 and then given a hormonal treatment (sufficient to maintain fetal viability) until Day 23. Cervical biopsies, taken from animals killed intrapartum or 1 h before expected parturition, were studied for eosinophilic infiltration and collagen birefringence. Intrapartum or sham-OVX pregnant rats showed a massive eosinophilic infiltration and a widespread collagenolysis as indicated by a loss of collagen birefringence. Ovariectomized pregnant rats treated with estrogen plus progesterone or with progesterone alone showed neither infiltration nor collagenolysis. In rats OVX during pseudopregnancy, estrogen given alone induced a significant infiltration of eosinophils in the cervical stroma; however, treatment with the combination of estrogen and progesterone was not able to promote eosinophilic infiltration. Collagenolysis was absent in all pseudopregnant animals. These results show that estrogen induced a cervical eosinophilic infiltration in rats but that when progesterone was added to the estrogen treatment the infiltration was not present; in addition, none of the steroid hormones assessed were responsible for the collagenolysis found in the cervical tissue at term.

Cytokine production at the site of disease in chronic eosinophilic pneumonitis.

Chronic eosinophilic pneumonitis (CEP) is characterized by longstanding respiratory symptoms accompanied by a massive pulmonary eosinophil infiltration. We hypothesized that cytokine(s) produced in the disease sites are implicated in the pathophysiology of CEP. We studied peripheral blood and bronchoalveolar lavage fluids (BALF) obtained from two lung segments of a patient with CEP. Seventy times more eosinophils were found in the BALF from an involved lung segment (showing patchy opacification on a chest roentgenogram) than from an uninvolved segment. The eosinophil-active cytokines interleukin-5 (IL-5), IL-6, and IL-10 were strikingly elevated in the BALF from the involved lung segment, whereas no or minimal levels of these cytokines were detectable in the BALF from the uninvolved segment or serum, respectively. Leukocytes in the involved lung segment, but not those in peripheral blood, expressed messenger ribonucleic acid (mRNA) for IL-5, IL-6, and IL-10. In contrast, IL-2, IL-3, IL-4, interferon-gamma (IFN-gamma), granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF-alpha) were not detected in any sample. These findings suggest that increased production of several cytokines, such as IL-5, IL-6, and IL-10, in the involved lung segment, but not in the uninvolved lung segment or peripheral blood, is a critical pathophysiologic feature of CEP.

Mouse Eotaxin Expression Parallels Eosinophil Accumulation during Lung Allergic Inflammation but It Is Not Restricted to a Th2-Type Response

A model of lung eosinophilia based on the repeated exposure of mice to aerosolized OVA has been used to identify C–C chemokine genes expressed at stages of massive eosinophil infiltration. We describe the identification and cloning of a cDNA that encodes a mouse C–C chemokine with 68% amino acid identity to guinea pig Eotaxin. The recombinant protein encoded by this gene displays potent and specific chemotactic activity for eosinophils, both in vivo and in vitro. Its mRNA levels parallel the kinetics of eosinophil accumulation in the lung during the experimentally induced eosinophilia and it is mainly produced by type I alveolar epithelial cells. The mRNA expression of mouse Eotaxin is not restricted to Th2 T cells in vitro and is independent of the development of a Th2-type response during N. brasiliensis infection, in vivo.

Massive eosinophilic infiltration in a patient with the nephrotic syndrome and drug-induced interstitial nephritis

The pathologic feature of acute interstitial nephritis is the infiltration of mononuclear cells, predominantly lymphocytes and monocytes, into the interstitium. We present an unusual case of a 49-year-old man with drug-induced acute interstitial nephritis whose renal biopsy specimen showed a massive infiltration of eosinophils into the interstitium and eosinophils infiltrating into the glomerulus through a gap in Bowman's capsule and the juxtaglomerular zone. The patient initially was referred to us with a recurrence of the nephrotic syndrome. Deterioration of renal function and an increase in proteinuria was noted at that time. Triazolam, a sleep inducer, was the suspected cause of the acute interstitial nephritis. Renal biopsy revealed sclerotic glomeruli containing eosinophils among massive infiltrated eosinophils and a loss of endothelial cells and mesangial cells in contrast to a preservation of epithelial cells. Infiltrating eosinophils were directly attached to the glomerular basement membrane, and free granules from the eosinophils were observed in the capillary lumen. In addition to chronic sclerotic change, eosinophils may have further damaged the glomerular capillary wall, leading to an increased severity of proteinuria in this case.

Pulmonary vasculitis with hypereosinophilia and episodic pulmonary hypertension: Report of three siblings

Three siblings with eosinophilia who developed pulmonary hypertension are reported. They consisted of a 3 year old boy (case 1), a 9 year old boy (case 2) and a 13 year old girl (case 3), all of whom died within an 18 month period of severe episodic attacks of pulmonary hypertension and the resultant low cardiac output. Marked peripheral eosinophilia was found in cases 1 and 2, and mild eosinophilia in case 3. Open lung biopsy of case 1 revealed pulmonary arteritis with massive eosinophilic infiltration and intimal thickening of muscular arteries of 300-1500 microns in diameter. At autopsy, cases 2 and 3 showed almost similar findings, comprising widespread obliteration of the pulmonary arteries by concentric intimal thickening, medial hypertrophy and recanalized thrombi of arterioles. Rarely, there were foci of granulomas in the thickened intima surrounding birefringent foreign bodies. There were small areas of infarction in the lungs and heart due to arterial thrombi. Vascular lesions other than those in the lungs were mild and almost limited to the branches of the coronary arteries. Therefore, the present cases appear to be a single disease of pulmonary hypertension secondary to endothelial injury and the resultant intimal fibrosis probably evoked by toxic substances, although such agents were not confirmed.

Eosinophilic Cystitis Caused by Vesical Sparganosis: A Case Report

We report a case of eosinophilic cystitis caused by vesical sparganosis. The patient had a history of eating raw frogs and presented with a mass in the bladder associated with peripheral eosinophilia and increased serum antibody titer against sparganum. Pathologically, a characteristic sinuous necrosis representing worm tracks was noted with massive diffuse infiltration of eosinophils in the wall of the bladder. The serum titer of sparganum-specific antibody returned to normal after surgical resection of the lesion. This finding emphasizes the importance of suspecting parasitic origin in cases of eosinophilic cystitis with a history of raw meat ingestion in endemic areas.

Granulomatous Arteritis with Massive Eosinophilic Leukocyte Infiltration and Transient Peripheral Eosinophilia Subsequent to Transarterial Embolization Therapy with a Gelatin Sponge

A 38-year-old man presented with a cavernous hemangioma in the liver. Transarterial embolization (TAE) using a gelatin sponge was carried out 14 days prior to surgical resection of the tumor. Granulomatous arteritis with massive infiltration by eosinophilic leukocytes and histiocytes was present at the periphery of the hemangioma, and transient eosinophilia in the peripheral blood occurred six days after resection. Granulomatous arteritis was evident in medium-sized arteries and there was narrowing or occlusion of the vascular lumen. In the granulomatous cellular infiltrates in the arteries, giant cells of the foreign body type were numerous. An eosinophilic substance differing from fibrin was present in some of the vascular lumina. As this showed staining for collagen, it was considered likely to be fragments of the gelatin sponge. The patient had no symptoms of fever, chills or general fatigue. The clinical course and pathologic findings suggest a causative role of the gelatin sponge in this case of granulomatous arteritis. Vascular change, a rare complication of TAE therapy, may be induced by a hypersensitivity reaction against the intra-arterial gelatin sponge.

Histopathological criteria for the diagnosis of abdominal angiostrongyliasis

An increasing number of cases of abdominal angiostrongyliasis have recently been diagnosed in southern Brazil. A comparative study of 19 confirmed cases and 15 suspected cases was undertaken to review the anatomo-pathology of the disease and to establish histopathological criteria for its diagnosis. The results were similar in both groups, except for the identification of the worm in the confirmed cases. Macroscopic features comprised two types: a predominant thickening of the intestinal wall (pseudo-neoplastic pattern) and a congestive necrotic lesion (ischemic-congestive pattern). Microscopically, three fundamental histopathological findings were detected: (1) a massive infiltration of eosinophils in all layers of the intestinal wall, (2) a granulomatous reaction and (3) eosinophilic vasculitis affecting arteries, veins, lymphatics and capillaries. We conclude that observation of this histopathological triplet excludes other causes of "eosinophilic gastroenteritis" and establishes the diagnosis of probable abdominal angiostrongyliasis.

好酸球性膀胱炎の2例

Two cases of eosinophilic cystitis are reported. Case 1 was a 7-year-old boy with pollakisuria and case 2 was a 20-year-old man with right lower abdominal pain. They were suspected of bladder sarcoma after the examinations by cystoscopy, IVP, ultrasonography, CT and NMR-CT. Transurethral, percutaneous and open biopsies were performed and histological examination revealed massive infiltration of eosinophils mainly in the vesical muscle layer without malignant cells. We could establish the diagnosis only by biopsy. In case 1, IgE RAST was positive for tick and case 2 seemed to be allergic to rare beef. We presumed that they caused eosinophilic cystitis.

Platelet-activating factor causes goblet cell depletion in the conjunctiva

Platelet-activating factor (PAF) (1-O-hexadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine) produced dose-dependent depletion of the goblet cell population associated with the conjunctival epithelium. Reductions in goblet cell numbers did not correspond to leukocyte infiltration and were consistent with a direct effect of PAF. In contrast, LTD 4 and LTE 4 did not affect the goblet cell population although they caused massive eosinophil infiltration into the conjunctival epithelium. Histamine also produced conjunctival goblet cell depletion, but this appeared secondary to eosinophil degranulation and resultant epithelial desquamation. In addition to globlet cell expulsion, PAF produced on increase in conjunctival microvascular permeability over an identical dose-range. PAF-induced leukocyte emigration was small or absent and comprised a neutrophil infiltrate which exhibited no clear dose-dependent relationship. Lyso-PAF produced effects only at the highest dose employed where pathological changes and a distinct increase in conjunctival microvascular permeability were evident. Lyso-PAF- and PAF-induced increases in conjunctival microvascular permeability were virtually abolished by the PAF antagonist CV-6209. The pronounced inhibitory activity of CV-6209 suggests that high doses of lyso-PAF may either weakly stimulate conjunctival PAF receptors or that there may be sufficient conversion of lyso-PAF to biologically active levels of PAF.

Intestinal pathology in human metagonimiasis with ultrastructural observations of parasites

A human case of intestinal metagonimiasis that was incidentally found during the histological examination of a resected segment of jejunum was described. The small adults trematode of Metagonimus yokogawai were found free in jejunal lumen as well as impacted in intervillous spaces. Histologically intestinal lesions were massive lymphoplasmacytic and eosinophilic infiltration in stroma, erosion of neanby enterocytes, goblet cell depletion and occasional villous edema. Scanning electron microscopy revealed the worm of spatulate appearance with rake-shaped tegumental spines. By transmission electron microscopy, the syncytial integument with dense discoidal bodies, basement membrane muscle cells and subtegumental cells were observed. Characteristic junctional complex was demonstrated between subtegumental and parenchymal cells as well as between parenchymal cells.

Interactions between granulocytes and platelets with the guinea-pig lung in passive anaphylactic shock. Correlations with PAF-acether-induced lesion.

To compare the bronchopulmonary effects of anaphylactic shock with those of platelet-activating factor (PAF-acether), antigen (ovalbumin) was administered intravenously to passively sensitized guinea-pig. Subsequent lung alterations were assessed histologically. Within 1 min following ovalbumin, bronchial and arterial constrictions were observed, accompanied by platelet thrombi in the pulmonary microcirculation, intravascular leucocyte accumulation with diapedesis, disruption of endothelium and alterations of type II pneumocytes. Free eosinophilic granules were scattered in the bronchial submucosa. One h after the infusion of ovalbumin, platelet aggregates had disappeared, bronchoconstriction was over, and denudation of the bronchial epithelium was observed. These alterations resemble to those induced by intravenous PAF-acether, which led us to compare the effects of inhaled PAF-acether and antigen at bronchoconstrictor concentrations. In both cases, leucocytes were aggregated in the microcirculation within 2 min and persisted 1 h later. Massive infiltration of eosinophils and activation and clumping of alveolar macrophages were also noted. Our findings support the involvement of PAF-acether in acute anaphylaxis in the guinea-pig.

Pyloric Obstruction Due to Muscular Hypertrophy and Massive Eosinophil Infiltration

Pyloric Obstruction Due to Muscular Hypertrophy and Massive Eosinophil Infiltration