PubMed · 10224433
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M M Glovsky, N Lukacs, P A Ward. Is complement activation a factor in bronchial asthma?. https://doi.org/10.1159/000024122
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Trichosanthin (TCS), the major effective component from Chinese herb Trichosanthes Kirilowii Maxim, is also a potent allergen. Our previous work has shown that TCS can upregulate interleukin-4 (IL-4) and interleukin-13 (IL-13) while inhibit interferon-gamma (IFN-gamma) in mesenteric lymph node cells after TCS immunization. Thus, TCS can arouse a T helper 2 (Th2) response in the draining lymph node. However, little is known about the early effects of TCS on antigen-presenting cells, the initiator of T cell response. In the current study, the effects of TCS on macrophage cytokines and chemokine expression were investigated. Peritoneal macrophages were treated with or without TCS in the presence of lipopolysaccharide (LPS). We found that TCS increased macrophage interleukin-10 (IL-10) and monocyte chemoattractant protein-1 (MCP-1) expression, whereas it decreased interleukin-12 (IL-12) and tumor necrosis factor-alpha (TNF-alpha) expression. Our study clearly demonstrated that TCS, as an allergen, has differential effects on macrophage Th1/Th2 initiative factors, effects that are likely to facilitate its inducing of Th2 and immunoglobulin E (IgE) response.
The cellular and molecular mechanisms involved in the airway hyperresponsiveness (AHR) of patients with allergic asthma remain unclear. A role for Th2 inflammatory cells was suggested based on murine asthma models. No direct evidence exists on the role of these cells in human asthma. The development of a mouse-human chimera might be useful, allowing the in vivo study of the components of the human immune system relevant to asthma. We investigated the role of allergen-reactive T lymphocytes in a human-mouse SCID model. SCID mice were reconstituted intratracheally with human PBMC from healthy, nonallergic, nonasthmatic donors and exposed to an aerosol of house dust mite allergen after i.p. injection with Dermatophagoides pteronyssinus I Ag and alum. The donor T lymphocytes had a Th1 cytokine phenotype. The reconstituted and allergen-challenged mice developed AHR to carbachol. The mouse airways and lungs were infiltrated with human T lymphocytes. No eosinophils or increases in human IgE were observed. The intrapulmonary human T lymphocytes demonstrated an increase in intracytoplasmic IL-4 and IL-5 and a decrease in IFN-gamma after exposure to allergen adjuvant. Antagonizing human IL-4/IL-13 or IL-5 resulted in a normalization of the airway responsiveness, despite a sustained intracellular Th2 cytokine production. These results provide evidence that the activated human allergen-reactive Th2 cells producing IL-4 or IL-5 are pivotal in the induction of AHR, whereas no critical role for eosinophils or IgE could be demonstrated. They also demonstrate that human allergen-specific Th1 lymphocytes can be driven to a Th2 phenotype.
Olive pollen allergy is a clinical disorder affecting the human population of Mediterranean areas. A novel major allergen, Ole e 9, has been isolated from olive pollen by gel permeation, hydrophobic affinity, and reverse-phase high performance liquid chromatographies. It is involved in the allergic responses of 65% of patients suffering olive pollinosis. Ole e 9 (molecular mass of 46.4 kDa) displays 1,3-beta-endoglucanase activity (38.9 +/- 5.6 mg of glucose released/min x micromol of protein at pH 4.5-6.0 using laminarin as substrate). It is the first 1,3-beta-glucanase, a member of the "pathogenesis-related" protein family, detected in pollen tissue. Seven tryptic peptides of the allergen were sequenced by Edman degradation and used for designing primers to clone the cDNA codifying the protein. Specific cDNA for Ole e 9 was synthesized from total RNA and amplified using the polymerase chain reaction. The allergen sequence showed an open reading frame of 460 amino acids comprising a putative signal peptide of 26 residues. It shows 39, 33, and 32% sequence identity including the catalytic residues when compared with 1,3-beta-glucanases from wheat, willow, and Arabidopsis thaliana, respectively. Northern blot analysis showed that Ole e 9 transcript is specifically expressed in the pollen tissue, and highly conserved counterparts were only detected in taxonomically related pollens.