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PubMed1994

Characterization of infiltrating CD4+ cells in atopic dermatitis using CD45R and CD29 monoclonal antibodies.

Tissue sections from the skin of patients with atopic dermatitis were investigated by means of hematoxylin-eosin staining, the avidin-biotin-peroxidase complex method, and double-labeling immunofluorescence using monoclonal antibodies to cell-surface antigens, including CD45R and CD29. In skin lesions of patients with atopic dermatitis, the epidermis was spongiotic and hyperplastic with little cellular infiltrate. Perivascular dermal infiltrate was significant and consisted primarily of mononuclear cells. The majority of the infiltrating mononuclear cells in the skin of patients with atopic dermatitis were CD4+ cells. Langerhans' cells were also increased in number. Furthermore, we investigated the subsets in the infiltrating CD4+ cells by double-labeling immunofluorescence using CD45R and CD29 monoclonal antibodies. Among the infiltrating CD4+ cells, CD4+CD29+ cells were dominant and CD4+CD45R+ cells were also present.

Adolescent↗

PubMed1995

Differences in E-selectin expression and leucocyte infiltration induced by inflammatory agents in a novel subcutaneous sponge matrix model.

We have developed a novel subcutaneous sponge matrix model in major histocompatibility complex (MHC) homozygous SLAb/b inbred pigs to study lymphocyte-endothelial cell interactions during inflammation. Polyether sponges were implanted subcutaneously and left for 12 days before injection of proinflammatory agonists. Implanted sponges became highly vascularized and showed markedly increased uptake of i.v.-injected 51Cr-labelled lymphocytes 5 hr after injection of tumour necrosis factor-alpha (TNF-alpha) (3000 U) or phytohaemagglutinin (PHA) (37 micrograms). Lower levels of traffic were seen in sponges 5 hr after injection with interleukin-1 alpha (IL-1 alpha) (3000 U) and no significant traffic occurred in sponges injected with phorbol 12-myristate 13-acetate (PMA) (15 ng) at 5 hr or PHA at 24 hr (compared to sponges injected with medium alone). Electron microscopy of control sponges revealed low numbers of infiltrating leucocytes and relatively 'flat' endothelium. Many more infiltrating leucocytes were present in PHA-injected sponges. However, no ultrastructural evidence was seen of any significant difference between control and activated endothelium. Immunocytochemistry of frozen sections from sponges showed that E-selectin expression was up-regulated markedly by TNF-alpha and PHA at 5 hr, only moderately by IL-1 alpha at 5 hr, and not at all by PMA at 5 hr. By 24 hr in PHA-injected sponges E-selectin expression had fallen markedly from the level seen at 5 hr. Flow cytometric analysis of cellular infiltrates dispersed from sponges injected with TNF-alpha, PHA, IL-1 alpha or medium alone, revealed differences in lymphocyte subset populations. The infiltrate in sponges injected with TNF-alpha 5 hr before removal was dominated by high numbers of CD2+ lymphocytes, whereas the infiltrate induced by PHA showed relatively higher levels of CD2- CD4-CD8- gamma delta T-cell receptor+ (TCR+) T cells revealed by population-specific monoclonal antibodies (mAb). This model, which permits harvesting of leucocytes and endothelial cells for manipulation in vitro, will be useful for the study of leucocyte-endothelial cell interactions in subacute and chronic inflammation.

Animals↗

PubMed1995

[Inflammatory cellular infiltration in scleritis].

BACKGROUND: Scleritis can be a destructive disease frequently associated with autoimmune disorders. It is believed that primary vasculitis plays an important role in its pathogenesis, but little is known about the cellular effector mechanisms. The purpose of this study was to analyze the inflammatory cellular infiltrate in scleritis. PATIENTS AND METHODS: Two enucleated eyes were studied. In one patient, enucleation was done after perforation occurred in anterior necrotizing scleritis and, in the other, after the misdiagnosis of posterior scleritis as an intraocular tumor. Morphological criteria and immunohistochemical methods were used to characterize the inflammatory cellular infiltrate. RESULTS: The cells infiltrating the scleral fibers in the enucleated eyes consisted predominantly of T cells in both cases; many of the T cells were CD4-positive. Clusters of B cells were found in perivascular areas. In circumscribed areas neutrophils, macrophages, and plasma cells were part of the scleral infiltrate. Signs of a granulomatous process with activated macrophages (epitheloid and giant cells) were present in necrotizing scleritis. Expression of major histocompatibility class II molecules (MHC II) was found on lymphocytes and rarely on macrophages. Signs of primary vasculitis were not found in any of the specimens. CONCLUSION: The cellular infiltrate in scleritis shows, at least at certain stages, features compatible with a T-cell mediated (autoimmune) disorder, which has major therapeutic implications.

Adult↗

PubMed1994

[Diagnosis and treatment of inflammatory infiltrates of the abdominal cavity in Crohn disease].

An infiltrate in the abdominal cavity in Crohn's disease does not hinder successful drug therapy in most cases. A positive effect (regression or a marked decrease in the size of the infiltrate) is achieved in 80% of patients, mostly in those with a moderately or mildly severe form of the disease in which a sufficiently prolonged, 10-12-week course of antiinflammatory treatment can be conducted. Combination of prednisolone with azathioprine and antibiotics is most justified. The prednisolone dose is determined by the severity and activity of the disease rather than by the infiltrate. Antibiotics are necessary only in high fever and treatment with them may be limited to 10-14 days in the absence of septicemia. Interrupted seasonal courses of sulfasalazine therapy may fail to prevent exacerbation and, consequently, recurrent infiltrates. These respond readily to repeated drug therapy and do not expand the indications for surgery. Operations were performed on 14 patients, in 11 of them the infiltrate did not recur again.

Abdomen↗

PubMed1994

[Treatment of lumbar facet joint syndrome by CT-guided infiltration of the intervertebral joints].

INTRODUCTION: Lumbar facet joint syndrome is a common condition, involving about 79% of patients suffering from low back pain. Denervation by scalpel or electrofrequency is a well-known method of treating it. An alternative method for longer lasting pain relief is CT-guided intraarticular infiltration of facet joints with local anaesthetics and cortisone. METHODS: In 62 patients with facet syndrome a total of 205 joints were infiltrated, CT monitoring being used in all cases. Each facet joint was infiltrated with 0.3 ml bupivacaine and 0.8 ml methylprednisolone. The patients were divided into three groups. Group 1 consisted of 24 persons who had undergone lumbar disc surgery, group 2 of 23 patients with spondylarthrosis of the facet joints, and group 3 of 15 patients who had undergone lumbar disc surgery but had additional spondylarthrosis. Very good results were defined as pain relief for longer than 4 weeks, good results as pain relief for up to 4 weeks and poor results as brief pain relief or none at all. In 27 patients facet infiltration was performed for the purpose of diagnosis. RESULTS: Results were significantly in group 2 than in group 1 (Fisher's exact test P < 0.012). In group 3 results were better than in group 1, but worse than in group 2. These differences were not statistical by significant (Table 3). Seven patients in the diagnostic group had no pain relief, and facet syndrome was excluded. CONCLUSIONS: CT-guided facet joint infiltration is a good method for treatment and diagnosis of lumbar facet joint syndrome. It can be repeated and has no severe side effects. The best results were seen in patients with spondylarthrosis of the facet joints. After lumbar disc surgery the pain relief was shorter, though it also yielded good results. For patients with unspecific low back pain, facet joint injections are a very good diagnostic method, allowing definite exclusion of lumbar facet syndrome.

Bupivacaine↗

PubMed1994

Cytokine expression, upregulation of intercellular adhesion molecule-1, and leukocyte infiltration in experimental tubulointerstitial nephritis.

BACKGROUND: Cytokines are intercellular polypeptide messengers that mediate immune and inflammatory responses. The temporal profile of interleukin-1 beta (IL-1 beta), IL-6, tumor necrosis factor alpha (TNF-alpha), and monocyte chemotactic protein 1 (MCP-1) expression was examined in anti-tubular basement membrane (TBM) antibody-associated tubulointerstitial nephritis (TIN). EXPERIMENTAL DESIGN: TIN was induced by immunization of Brown Norway rats with bovine cortical TBM, whereas control rats received ovalbumin. Whole kidney RNA was assessed with the RNase protection assay 3, 7, 8, 9, 10, 12, and 14 days after immunization. Cytokine mRNA expression was correlated with TNF-alpha bioactivity, renal intercellular adhesion molecule-1 expression, and CD18-positive leukocyte infiltration by immunohistochemistry. RESULTS: Increased IL-1 beta, TNF-alpha, and MCP-1 mRNA relative to glyceraldehyde-3-phosphate dehydrogenase appeared on day 7 when TIN involved 10 to 40% of the cortex, and peaked rapidly on day 8 when there was 60 to 80% cortical involvement (at which time 75 to 80% of the infiltrating cells were neutrophils). The increase in TNF-alpha mRNA correlated with increased bioactivity. The influx of mononuclear cells on day 8 was preceded by the expression of MCP-1 mRNA. The infiltrating leukocytes expressed the leukocyte beta 2-integrin (CD18) and were found in areas with increased intercellular adhesion molecule-1 expression. The mRNAs for IL-1 beta, TNF-alpha, and MCP-1 were undetectable by day 10 (at which time 95% of the infiltrating cells were mononuclear). An increase in IL-1 receptor antagonist mRNA paralleled those of IL-1 beta. The expression of IL-6 mRNA was similar to that for IL-1, except that it disappeared by day 9. CONCLUSIONS: There is a temporal association in the expression of IL-1 beta, TNF alpha, MCP-1, and IL-6 with the upregulation of intercellular adhesion molecule-1 and leukocyte infiltration within the tubulointerstitium in anti-TBM antibody-associated TIN. The narrow window of time through which these cytokines are expressed and the coincidence of their peak expression on day 8 suggest complex cytokine interactions in the pathogenesis of anti-TBM antibody TIN.

Animals↗

PubMed1994

[Macrophage infiltration in IgA nephropathy and Henoch-Schönlein purpura nephritis--1. Relationship to clinicopathological findings].

Renal biopsy specimens from 42 children with IgA nephropathy and 23 with Henoch-Schönlein purpura nephritis (HSPN) were examined to investigate the relationship between intraglomerular and interstitial infiltrating macrophage populations and their clinicopathological findings. Macrophages were stained by monoclonal antibody (CD68) using the ABC method. Intraglomerular and interstitial macrophages were significantly increased in HSPN (2.48 +/- 2.71/glomerular cross-section: gcs, 11.54 +/- 11.67/mm2) compared with IgA nephropathy (1.36 +/- 1.09/gcs, 5.30 +/- 4.53/mm2). Infiltrating macrophages were significantly increased in both renal disease compared with minimal change nephrotic syndrome (0.29 +/- 0.12/gcs, 1.36 +/- 0.82/mm2). Infiltrating macrophages tended to decline with the lapse of time between the renal biopsy and the discovery of the renal disease, especially in HSPN. Increase in glomerular macrophages in HSPN was associated with the severity of their clinicopathological findings, but this was not the case in IgA nephropathy. Interstitial macrophages were increased in patients with severe clinicopathological findings in both disease. Patients having both proteinuria and hematuria showed many infiltrating macrophages compared to those with proteinuria or hematuria alone. These findings suggest that intraglomerular and interstitial infiltrating macrophages play important roles in the acute and early phase of IgA nephropathy and HSPN in children.

Adolescent↗

PubMed1994

Persistent indurated plaques of the face: a variant of Jessner's lymphocytic infiltrate?

Lymphocytic infiltrates of the skin classically include a select number of diagnostic entities such as lupus erythematosus, gyrate erythema, polymorphous light eruption, lymphocytoma cutis, lymphocytic leukemia, and lymphocytic infiltrate of Jessner. We recently observed two patients with chronic inflammatory plaques of the face with histologic features of a lymphocytic infiltrate with unusual clinical features. Persistent indurated plaques of the face may be a manifestation of lymphocytic infiltration of the skin that could represent a variant of Jessner's lymphocytic infiltrate. Cases may be refractory to all forms of treatment other than systemic corticosteroids. Clinicians should be aware of this variant and exclude lupus erythematosus and photodermatitis.

Adult↗

PubMed1993

Carcinomatous invasion and lymphocyte infiltration in early esophageal carcinoma with special regard to the basement membrane. An immunohistochemical study.

We examined 24 cases of superficial esophageal carcinoma and evaluated 94 areas, including 43 intra-epithelial (ep), 36 mucosal (m) and 15 submucosal (sm) areas, using the immunohistochemical staining of laminin to detect the basement membrane. The staining pattern was divisible into three patterns, i.e., continuous, fragmentary and defective. Defective patterns were observed in 14%, 53%, and 73% of the ep, m, and sm lesions, respectively (p < 0.01). With regard to the degree of lymphocyte infiltration, 77% of the continuous areas were accompanied by a low lymphocyte infiltration, while 56% of the defective areas were accompanied by dense infiltrations with follicle formation. Lymphocyte infiltration was thus statistically significantly (p < 0.01) more closely associated with the defective areas than with the continuous areas. Furthermore, urokinase-type plasminogen activator was detected immunohistochemically in 11.1% of the defective areas, and in none of the continuous areas. These findings suggested 1) that superficial esophageal carcinoma might progress while destroying the basement membrane, and 2) that as host immune reactions lymphocytes might infiltrate the lesions where the basement membranes were destroyed and cancer cells exposed to the underlying layer. The findings also suggested the possibility that the degradation of the basement membrane might be caused by proteolytic enzymes produced by cancer cells.

Adult↗

PubMed1995

An analysis of prognostic features in infiltrating lobular carcinoma of the breast.

To establish prognostically useful pathologic features for infiltrating lobular carcinoma, histologic pattern, nuclear Grade 1 or 2, lymphatic invasion, the presence and extent of lobular carcinoma in situ, estrogen and progesterone receptor status, axillary lymph node status, tumor size, and pathologic stage were assessed as prognostic variables in 92 cases of infiltrating lobular carcinoma. Clinical follow-up was obtained (mean duration, 5.2 yr), and patients were classified as alive with no evidence of disease, alive with disease, or dead of disease. Recurrence (alive with disease and dead of disease) was associated with axillary lymph node metastases (P = 0.04), tumors measuring > 1.0 cm (P = 0.008), and pathologic Stage III/IV disease (P = 0.033). Survival (no evidence of disease and alive with disease) was associated with Stage I/II disease (P = 0.003). Statistically insignificant associations with disease recurrence or survival follow: infiltrative pattern (classical, alveolar, solid, mixed), nuclear grade, lymphatic vessel invasion, presence of lobular carcinoma in situ, extent of lobular carcinoma in situ (< 25% or > or = 25%), and hormone receptor status. Many of the prognostic features used in ductal carcinoma do not appear to be applicable to infiltrating lobular carcinoma. However, tumor size, axillary node status, and pathologic stage are prognostically useful in infiltrating lobular carcinoma.

Axilla↗

PubMed1996

Comparison of topical anesthetics without cocaine to tetracaine-adrenaline-cocaine and lidocaine infiltration during repair of lacerations: bupivacaine-norepinephrine is an effective new topical anesthetic agent.

OBJECTIVE: To compare the effectiveness of four topical anesthetics that do not contain cocaine with that of topical tetracaine-addrenaline-cocaine (TAC) and lidocaine infiltration during laceration repair in children. DESIGN: This was a randomized, blinded trial. SETTING: The study was conducted in the emergency department of a large children's hospital. PARTICIPANTS: Subjects were children 2 years of age or older with a laceration 5 cm or less in length that required sururing. INTERVENTIONS: Patients were randomly assigned to receive one of four noncocaine-containing topical anesthetics, topical TAC, or lidocaine infiltration anesthesia before laceration repair. OUTCOME MEASURES: Outcome measures assessed pain perceptions using a Visual Analogue Scale, Likert scale, and Anethetic Effectiveness scale. Distress behaviors of patients were measured with the Restrained Infants and Children Distress Rating Scale. RESULTS: Two hundred forty patients were enrolled in the study. Using alpha = 0.05 and beta = 0.2, there was statistical power to detect differences of 0.3 to 1.3 U for the outcome measures used. The bupivacaine-norepinephrine topical solution (Bupivanor) performed better than the other three new topical preparations. It provided effective wound anesthesia during lacertion repair, especially for lacerations of the face and scalp, where it was consistently rated as effective as TAC and 1% lidocaine infiltration by all observer groups for all outcome measures. There was a 4% overall wound complication, including one wound infection. CONCLUSION: Bupivanor is an effective alternative to TAC and lidocaine infiltration for local anesthesia during laceration repair, expecially on the face and scalp. The effectiveness of Bupivanor on the face is important, because it is here where TAC is most likely inadvertently to come into contact with mucous membranes and result in systemic toxicity. Because pain and distress scores did not take into consideration the pain associated with the initial injection of lidocaine, the findings of this study conservatively estimate Bupivanor's effectiveness, compared with lidocaine infiltration.

Administration, Cutaneous↗

PubMed1996

[T cell lymphoma presenting as recurrent bilateral pulmonary infiltrates over five years].

A 52-year-old man presented with BOOP-like recurrent bilateral pulmonary infiltrates. In 1989 a chest X-ray film showed an infiltrative shadow in the right S6 region which disappeared after administration of prednisolone. Thereafter, bilateral patchy infiltrates recurred many times, and each time they resolved rapidly with steroid therapy. Skin eruptions on the face recurred. In October 1994 the patient underwent an open-lung biopsy of the infiltrate in the left S6 region. The pathological findings were consistent with BOOP, except for the moderate-to marked infiltration of lymphocytes. A lymphoproliferative disorder was suspected, and Southern blot analysis of the specimen revealed a rearrangement of the TCR-beta gene, which led to the diagnosis of T cell lymphoma. Ten months after the diagnosis, no recurrence of the lymphoma had been detected. In this case a gene analysis of the biopsy specimen was very useful for the diagnosis of T cell lymphoma.

Cryptogenic Organizing Pneumonia↗

PubMed1996

Resident and infiltrating immune cells in the uveal tract in the early and late stages of experimental autoimmune uveoretinitis.

PURPOSE: To investigate the dynamics of resident and infiltrating immune cells in the choroid and iris during the early and late stages of experimental autoimmune uveitis (EAU) in Lewis rats. METHODS: Uveoretinitis was induced by footpad injection of crude retinal extract and complete Freund's adjuvant with concurrent intraperitoneal injection of Bordetella pertussis. Five experimental (EAU) and five control animals (adjuvant alone) were studied at days 5, 7, 9, 11 (prodromal stage) and 42 (late stage) after immunization. Five normal animals and five animals injected with B. pertussis alone served as further controls. Immunohistochemical localization of resident macrophages, major histocompatibility complex class II (Ia)+ dendritic cells (DC), infiltrating mononuclear cells, and T cells was performed on wholemounts of isolated choroidal and iris tissue. RESULTS: Double immunolabeling confirmed the presence of distinct networks of macrophages (591 +/- 52 cells/mm2) and DC (746 +/- 38 cells/mm2) in the rat choroid. No marked qualitative and quantitative changes were observed in the density or morphologic appearance of ED2+ resident tissue macrophages in the choroid and iris before clinical onset of ocular disease. On day 11, infiltration of ED1+ monocytes had occurred in the iris but not in the choroid; however, marked infiltration of T cells was evident in both choroid (286 +/- 161 cells/mm2) and iris (196 +/- 72 cells/mm2). The total density of Ia+ cells was significantly elevated in the choroid (1152 +/- 192 cells/mm2) at day 11, and small, round Ia+ cells were two to three times more frequent than normal at both sites. The density of T cells and Ia+ cells remained significantly elevated in the choroid and iris in the late stages of EAU. CONCLUSIONS: These data suggest resident uveal tract macrophages undergo no significant alteration in density in the early stages of EAU and that the earliest site of mononuclear cellular infiltrate in EAU occurs in the iris. The increased total density of Ia+ cells in the choroid on day 11 and the presence of significantly increased numbers of small, round Ia+ cells in the iris and choroid may represent increased trafficking of DC in the eye during uveoretinitis. Furthermore, the raised numbers of Ia+ cells, concurrent with the influx of T cells, suggests Ia+ DC and macrophages may act as local antigen-presenting cells in the induction of uveoretinitis.

Animals↗

PubMed1996

Decreased reflex tearing is associated with lymphocytic infiltration in lacrimal glands.

OBJECTIVE: To investigate whether reflex tearing measured by the Schirmer test with nasal stimulation is better correlated with lymphocytic infiltration of the lacrimal gland and is thus a more appropriate test for Sjögren's syndrome (SS). METHODS: 272 patients with dry eye (age 55.5 +/- 13.5 years) with regular Schirmer test results < 10 mm were recruited for the study. They were divided into 2 groups depending on the results of the Schirmer test with nasal stimulation. 24 age and sex matched patients from each group were selected for lacrimal gland biopsy and 10 patients for salivary gland biopsy, and the levels of systemic autoantibodies and degrees of ocular surface staining and lymphocytic infiltration of the lacrimal and salivary glands were compared. RESULTS: Of the 272 patients, 187 (68.8%) had good reflex tearing (GT) and 85 (31.2%) had poor reflex tearing (PT). There were no significant differences in the age or sex of the 2 groups. Lymphocytic infiltration of the lacrimal gland was observed in 7 GT cases and 22 PT cases out of 24 cases. Lymphocytic infiltration of the salivary gland was also higher in the PT (6 of 10) than the GT group (2 of 10). CONCLUSION: Evaluation of reflex tearing by the Schirmer test with nasal stimulation identifies 2 groups of patients with dry eye. Those with poor reflex tearing were more likely to have autoantibodies and lymphocytic infiltration of the exocrine glands consistent with SS.

Adult↗

PubMed1997

Immunologic and virologic characterization of the primary infiltrating cells in the aqueous humor of human T-cell leukemia virus type-1 uveitis. Accumulation of the human T-cell leukemia virus type-1-infected cells and constitutive expression of viral and interleukin-6 messenger ribonucleic acids.

PURPOSE: To characterize immunologically and virologically the infiltrating cells in the aqueous humor of patients with human T-cell leukemia virus type-1 (HTLV-1) uveitis (HU). METHODS: With their informed consent, patients had 0.1 ml of the aqueous humor in the anterior chamber collected with a needle under an operating microscope. An aliquot of the collected sample from patients without steroid therapy was examined by May-Giemsa staining and immunocytochemically. The presence of the HTLV-1-infected cells was investigated by polymerase chain reaction (PCR) using the gag and pol regions of the provirus genome. The population of the infected cells was compared by PCR testing the amplification of the virus genome from 60 cells, or determining the endpoint of successful amplification of the twofold dilution series of the samples, collected from the aqueous humor and peripheral blood mononuclear cells (PBMCs), which were obtained at the same time. Expression of viral and cytokine genes was studied by reverse transcriptase-PCR (RT-PCR). The interleukin-6 (IL-6) level in the aqueous humor of patients with HU and control subjects was measured by a high-sensitivity enzyme-linked immunosorbent assay kit. RESULTS: The number of the infiltrating cells ranged from 475 to 3563 (mean = 2111) per 0.1 ml of aqueous humor, and all the identifiable cells were lymphocytes. Most of them were CD3-positive T cells (mean = 78%), whereas CD4-positive cells constituted less than half (mean = 35.3%). HTLV-1 provirus was detected by PCR in the infiltrating cells of 36 of 38 patients with HU tested, whereas it was detected in 1 of 4 seropositive patients with other entities of uveitis. A higher population of the infected cells in the aqueous humor than in the PBMC was found in seven of nine patients with HU by two independent approaches. Expression of HTLV-1 env or pX genes or both was shown in all 12 patients with HU tested by RT-PCR. IL-6 messenger ribonucleic acid (mRNA) was detected by RT-PCR in 10 of these 12 patients, whereas those of interleukin-1 alpha, interleukin-2, interleukin-4, and tumor-necrosis factor-alpha were not, and that of interferon-gamma was detected in only 1 patient. The IL-6 level was elevated significantly in the aqueous humor of nine patients with HU compared with that of five control subjects (520.2 +/- 841 pg/ml versus 2.77 +/- 1.59 pg/ml, P < 0.01 by Mann-Whitney test). CONCLUSIONS: HU is characterized by lymphocytic infiltration with a predominance of T cells and by the presence and probable accumulation of HTLV-1-infected lymphocytes in the affected eye. Production of viral antigens and IL-6 by the infiltrating cells could be responsible for the development of HU.

Adult↗

PubMed1997

[The inhibitory effect of LTB4 antagonist on eosinophil infiltration in cutaneous and gut late phase response in BALB/C mice sensitized with ovalubumin (OVA)].

In this study we investigated the effect of LTB4 antagonist on eosinophil infiltration in skin and gut late phase response (LPR) in OVA-sensitized BALB/c mice. The eosinophil infiltrations to skin and gut induced by skin and oral challenge reached a peak at 12 h and 6 h after the challenge, respectively. Intraperitoneal administration of LTB4 antagonist (ONO-4057) before the challenge significantly inhibited eosinophil infiltrations to the skin and gut by 53.3% and 73.7%, respectively (p < 0.05). Next, we investigated the effect to that by PAF antagonist (ONO-6240) and anti-IL-5 mAb in the skin system. OVA-induced eosinophil infiltration at 12 h after intracutaneous challenge was significantly inhibited by peritoneal administration of anti-IL-5 mAb before the challenge by 89.6% (p < 0.05), but not by that of PAF antagonist. Our results demonstrated the inhibitory effect of LTB4 antagonist on eosinophil infiltration in skin and gut LPR, suggesting the potency of LTB4 antagonist for treatment of skin lesion and food allergy in atopic dermatitis considered to be associated with LPR.

Animals↗

PubMed1997

Histological evidence of neuraminidase involvement in acute nephritis: desialized leukocytes infiltrate the kidney in acute post-streptococcal glomerulonephritis.

Serum neuraminidase (NA, sialidase) activity has been demonstrated in acute poststreptococcal glomerulonephritis (APSGN) and implicated in the pathogenesis of the disease. Recent investigations show that neuraminidase-treated leukocytes accumulate preferentially in kidneys; therefore, we were interested in knowing if desialized cells infiltrate the kidney in APSGN. We first tested the capacity of peanut agglutinin lectin (PNA) to detect injected NA-treated leukocytes in the kidney of rats. NA-treated leukocytes were transfused and desialized cells were identified with fluorescein-conjugated peanut lectin (FITC-PNA) in renal tissue. PNA positive cells were identified in rat kidneys 3 hours after injection (glomeruli: 1.67 +/- 0.19 cells/g.c.s.; interstitium: 0.50 +/- 0.12 cells/int). Sections from available renal biopsy material of APSGN (n = 11), other glomerulonephritis (n = 28) and normal kidneys (n = 5) were double-stained with FITC-PNA and with monoclonal antibody to the CD11b molecule, which is expressed on polymorphonuclear and monocytes the main types of infiltrating cells during APSGN. Desialized (FITC-PNA positive) cells were found in the glomeruli (2.17 +/- SEM 0.22 cells per glomerular cross section, g.c.s.) and interstitium (0.61 +/- 0.15 cells per 0.0625 mm2, int) in all biopsies of APSGN. Only in 2 of 28 other glomerulonephritis showed desialized cells. More than 80% of the PNA positive cells in APSGN expressed the CD11b molecule and the infiltration was more intense in early biopsies. In conclusion, desialized leukocytes represent a significant part of the inflammatory infiltrate in APSGN. This finding gives support for a role of NA in the disease and provides clinical validation for a mechanism of renal cellular infiltration suggested by experimental observations.

Animals↗

PubMed1997

Chronic expression of murine flt3 ligand in mice results in increased circulating white blood cell levels and abnormal cellular infiltrates associated with splenic fibrosis.

The effect of chronic expression of flt3 ligand (FL) on in vivo hematopoiesis was studied. Retroviral vector-mediated gene transfer was used in a mouse model of bone marrow transplantation to enforce expression of mouse FL cDNA in hematopoietic tissues. As early as 2 weeks posttransplantation, peripheral blood white blood cell counts in FL-overexpressing recipients were significantly elevated compared with controls. With the exception of eosinophils, all nucleated cell lineages studied were similarly affected in these animals. Experimental animals also exhibited severe anemia and progressive loss of marrow-derived erythropoiesis. All of the FL-overexpressing animals, but none of the controls, died between 10 and 13 weeks posttransplantation. Upon histological examination, severe splenomegaly was noted, with progressive fibrosis and infiltration by abnormal lymphoreticular cells. Abnormal cell infiltration also occurred in other organ systems, including bone marrow and liver. In situ immunocytochemistry on liver sections showed that the cellular infiltrate was CD3+/NLDC145+/CD11c+, but B220- and F4/80-, suggestive of a mixed infiltrate of dendritic cells and activated T lymphocytes. Infiltration of splenic blood vessel perivascular spaces resulted in vascular compression and eventual occlusion, leading to splenic necrosis consistent with infarction. These results show that FL can affect both myeloid and lymphoid cell lineages in vivo and further demonstrate the potential toxicity of in vivo treatment with FL.

Animals↗