Mast cell heterogeneity: Evidence and implications

Mast cells and basophils play a fundamental role in the pathogenesis of allergic disease, although their physiologic role is largely unknown. A large body of evidence now indicates that the properties of mast cells are dependent on the tissue and species from which they are derived. Such mast cell heterogeneity encompasses differences in morphology, development, cytochemistry, and function. The evidence for such heterogeneity, and some of its clinical implications, is discussed.     

Negative regulatory effect of histamine in DNFB-induced contact hypersensitivity

Histamine plays an important role in the regulation of various immunological functions. To evaluate the role of histamine in contact hypersensitivity, contact dermatitis was induced with dinitrofluorobenzene (DNFB) in histidine decarboxylase knockout (HDC-/-) histamine-deficient and wild-type mice. The DNFB-induced increase of the ear thickness was significantly higher in HDC-/- mice than in wild-type mice. Using flow cytometry, significantly lower percentages of CD4+ Th and CD8+ Tc cells, and significantly higher percentages of CD45R+ B cells were observed in the regional lymph nodes in HDC-/- mice than in wild-type mice. In the ear specimens of both groups, the majority of the infiltrating cells were neutrophils and macrophages at 24 and 48 h after challenge. Using immunohistochemistry, we observed significantly more CD45+ leukocytes in HDC-/- mice than in wild-type mice. The expression of Th1 (IL-2, IFN-gamma, TNF-alpha) and Th2 (IL-4) mRNAs was examined by quantitative real time RT-PCR in the ear samples. The levels of Th1 cytokine mRNAs both at 24 and 48 h after challenge and IL-4 mRNA at 48 h showed a significantly higher increase in HDC-/- mice than in wild-type mice. These results suggest that histamine plays a negative immunoregulatory role in DNFB-induced contact hypersensitivity.     

Mast cell–derived IL-13 downregulates IL-12 production by skin dendritic cells to inhibit the TH1 cell response to cutaneous antigen exposure

1. Download : Download high-res image (242KB)
2. Download : Download full-size image

     

Rush desensitization in heparin hypersensitivity: a case report

Among all the known drug intolerances, adverse reactions to heparin are not very common. No desensitization in patients with heparin hypersensitivity has ever been attempted. We report the case of a 55–year-old female patient with mitral stenosis and insufficiency, and tricuspid and aortic insufficiency. The patient underwent heparin treatment, and urticaria occurred with either s.c. calcium heparin or i.v. sodium heparin. Allergy testing (skin tests and patch tests) was negative. A pseudoallergic intolerance was diagnosed. Mitral valve replacement with the extracorporeal circulation method was necessary; therefore, heparin treatment was administered. A heparin rush desensitization together with antihistamine drugs (4 mg clorpheniramine maleate for 3 d) was started: 50 UI (0.5 mg) s.c. sodium heparin were first administered; within 4 d, 5000 UI (50 mg) sodium heparin was administered i.v. with no side-effects. A full-dosage heparin treatment was then administered and heart surgery was easily performed. During the postsurgical course, i.v. sodium heparin was smoothly replaced with s.c. calcium heparin (25000 UI s.c. per day) and with oral anticoagulants (sodium warfarin).     

HLA class II haplotypes associated with pulmonary interstitial lesions of polymyositis/dermatomyositis in Japanese patients

To elucidate the immunogenetic background of idiopathic inflammatory myopathies (IIM) such as polymyositis (PM), dermatomyositis (DM) and any overlapping subsets, with other collagen vascular diseases, HLA class I antigens and class II alleles were determined and compared from individuals with various clinical and serological features of IIM, including pulmonary interstitial lesions (PI). Seventy-three Japanese patients with myositis (32 PM, 18 DM, 23 overlapped subsets) and 62 healthy unrelated controls were enrolled onto the study. Statistical differences between groups were determined by the Fisher's exact probability test. Serum fluorescent antinuclear antibody, rheumatoid factor (RF), anti-SS-A/Ro antibody, anti-Jo1 antibody and anti-U1 RNP antibody were examined using routine methods. PI was detected by chest X-ray and/or computed tomography. In patients with DM, the frequency of the HLA-DRB1*1302-DQA1*0102-DQB1*0604 haplotype was significantly higher than in the healthy controls (42.1% vs 17.7%), and in the patients with PM (42.1% vs 9.4%). Furthermore, the frequency of the HLA-DRB1*0405-DQA1*03-DQB1*0401 haplotype was higher in the PM patients with PI than in the controls (50.0% vs 17.7%), and PM without PI (50.0% vs 5.5%). These results suggest that in terms of HLA class II association, Japanese DM and PM, and PM with and without PI, belong to different clinical groups.     

Influence of maternal infections with viral agents or Toxoplasma gondii during pregnancy on fetal IgE production

The importance of maternal infections with Toxoplasma gondii , cytomegalovirus (CMV), Parvovirus B19, respiratory syncytial virus (RSV), and influenza A and B on fetal IgE synthesis was studied in 153 pregnant women. No case of specific IgM activity or viral DNA in cord blood, indicating a congenital infection, was found. From gestational week 15 to delivery, maternal IgG-Ab seroconversion to Parvovirus B19, RSV, influenza A, or influenza B occurred in 47 women. At delivery, serologic signs of past infection with T. gondii were observed in 29 (19%) women, and the corresponding figure for CMV was 117 (77%). The number of women with positive IgG seroconversion during pregnancy or positive IgG-Ab activity toward the studied infectious agents at delivery did not differ significantly among infants with an increased (≥1.3 kU/1; n =51) or with an undetectable (<0.1 kU/l; n =102) cord-blood IgE level. These results show that genetic and other environmental factors probably have a greater influence on fetal IgE synthesis than do maternal infections during pregnancy.     

Correlation between cyclophosphamide-induced viral susceptibility and depletion of Junin virus-induced suppressor populations.

In contrast to lymphocytic choriomeningitis virus, another arenavirus, Junin virus (JV), the etiologic agent of Argentine hemorrhagic fever, when inoculated into suckling mice, induces lethal meningoencephalitis characterized by a delayed-type hypersensitivity (DTH)-like immune response. However, the adult BALB/c mouse is resistant to infection and no DTH reaction can be seen. This different viral sensitivity may be related to the development of an antigen non-specific DTH-suppressor cell pathway at work in the adult mouse. When the resistant mice are treated with cyclophosphamide (Cy) (50 mg/kg each dose) given at days -1,+1,+4 (zero: infection day), animals become susceptible and develop DTH reaction in brain that leads to death. We analyze the influence of the timing of Cy administration on the suppressor system developing after infection. It was found that Cy depletes the previously described JV-induced suppressor populations (Tsv) but a new suppressor cell (Tsv*) is disclosed bearing the Thy 1+ Ly1+2- phenotype which is unable to depress DTH in Cy-treated animals. With only two doses of Cy corresponding to days -1 and +1, the target of Tsv* cells is depleted but the third dose is still required to achieve full depletion of Tsv cells which are able to employ the Cy-resistant antigen-specific suppressor cells as targets. Since the Cy treatment is able to deplete the Tsv population together with the target of Tsv* cells, animals became unable to regulate lethal DTH reaction. Thus, a cellular explanation for an empirically established Cy schedule able to abrogate the adult mouse resistance to JV is proposed.     

Flow-Cytometric Analysis of Human Basophil Degranulation

Quantification of human basophils and their degranulation were performed using a flow-cytometric system. It was shown that the number of basophils among total leukocytes, before and after the effect of degranulating agents, can be obtained rapidly and reproducibly, following alcian blue, staining. Dose-response curves of degranulation by anti-IgE and anti-IgG₄ were studied, and it was shown that these antibodies can induce basophil degranulation in a Ca⁺⁺ dependent manner. It was also shown that degranulation is completed within 10 min.
Values obtained by flow-cytometry and microscopic evaluation, as well as comparison made between percent basophil degranulation and percent histamine release, agreed well with each other in our system. Flow-cytometric analysis of human basophil degranulation provides a new reliable method to assess in vitro the morphological basis of immediate hyper-sensitivity.