Inflammatory mediators of asthma: an update.

Pharmacology of the Eosinophil

In order to determine the role of CD4+ and CD8+ T-cells and of interleukin-5 (IL-5) in causing antigen-induced eosinophil infiltration into the site of airway late-phase reaction, we examined the effect of the in vivo depletion of CD4+ and CD8+ T-cells on the eosinophil infiltration of the trachea induced by antigen inhalation in mice. We also studied the effect of anti-murine IL-5 monoclonal antibody (mAb) on the antigen-induced eosinophil infiltration in the trachea. The eosinophil infiltration into the trachea of ovalbumin (OVA)-sensitized BALB/c mice began to increase 9 h after OVA inhalation and persisted for more than 48 h. The in vivo depletion of CD4+ T-cells by pretreatment with anti-L3T4 mAb significantly decreased the eosinophil infiltration induced by OVA inhalation in the trachea of sensitized mice. However, the in vivo depletion of CD8+ T-cells by pretreatment with anti-Lyt-2 mAb had no significant effect on OVA-induced eosinophil infiltration in the trachea. Pretreatment with anti-murine IL-5 mAb also decreased OVA-induced eosinophil infiltration in the trachea. In contrast, neither disodium cromoglycate nor a selective antagonist for platelet-activating factor CV-6209 decreased OVA-induced airway eosinophilia in the mouse. Our results provide direct evidence that CD4+ but not CD8+ T-cells mediate antigen-induced eosinophil recruitment in the airways and that IL-5 mediates this eosinophil recruitment.

CD4+ T-lymphocytes and interleukin-5 mediate antigen-induced eosinophil infiltration into the mouse trachea.

Platelets exhibit archetypal structures and functions enabling their roles as multifunctional host defense cells. Beyond roles in hemostasis and wound repair, platelets sense and respond to pathogens through mechanisms including pattern recognition, early trafficking to sites of infection, direct antimicrobial functions, and potentiation of innate and adaptive immune mechanisms. Insufficient platelet quantity and dysfunctions in platelet quality increase the risk of infections or worsen severity. Moreover, certain pathogens may subvert the host defense functions of platelets, exploiting them in pathogenesis. Here, the immunobiology of platelets in antimicrobial host defense is reviewed from each of these perspectives.

The role of platelets in antimicrobial host defense.

Many different mediators have been implicated in allergic responses and allergic diseases.14 It is becoming increasingly apparent that no single mediator can account for allergic diseases, such as asthma, rhinitis, eczema, or anaphylaxis, and that the clinical manifestation depends on a complex interaction of mediators that are released from a variety of cells. Although previous research concentrated on the mast cell as the key cell in allergic reactions, it now appears likely that other inflammatory cells, such as macrophages, eosinophils , neutrophils, platelets, and lymphocytes, may also contribute to the inflammatory response. The recognition that cells, other than mast cells, such as eosinophils,5 platelets,6 and macrophages,7 may be activated by IgE-dependent mechanisms has focused attention on these other cells as sources of mediators. Histamine,8 prostaglandinsg and leukotrienes3 have been previously proposed as playing a role in mediating allergic responses. Another mediator that is receiving increasing attention is PAF, a highly potent inflammatory mediator formed, like prostaglandins and leukotrienes, by the action of phospholipase A, on membrane phospholipids. The purpose of this article is to review the various effecs of PAF that may be relevant to allergic diseases and to speculate on its possible involvement in allergy. With the introduction of specific PAF antagonists during the next few years, the role of this inflammatory mediator will be clarified. had previously been demonstrated in the rabbit that platelets provided the major source of histamine among the blood elements,” but it was not known whether histamine release during allergen challenge represented a direct or indirect consequence of the recognition of allergen by antibody. Histamine release in sensitized rabbits undergoing antigen challenge was demonstrated to be the consequence of IgE-dependent activation of basophils that, in turn, released a soluble product capable of eliciting platelet activation.““S ‘* This product was termed PAF and was subsequently demonstrated to be a phospholipid.‘3 The chemical structure was then identified in 1979 by three independent groups as 1-o-alkyl-2-acetyl-sn-glyceryl-3phosphorylcholine (Fig. 1). 14-16 This phospholipid has been variously referred to as PAF-acether,14 acetyl glyceryl ether phosphorylcholine,‘5 or antihypertensive polar renomedullary lipid.16 The original nomenclature (PAF) will be used throughout this article, although it is now apparent that PAF has many other actions in addition to activation of platelets.

https://www.jacionline.org/article/0091-6749(88)90952-9/pdf

Platelet-activating factor as a mediator of allergic disease

Intravenous administration of PAF-acether to the guinea pig induces bronchoconstriction, hypotension, intravascular platelet aggregation, endothelial disruption, and platelet and neutrophil diapedesis. These effects are followed within 1 h by an eosinophilic infiltration into the bronchial walls, which was also noted after the administration of antigen to passively sensitized guinea pigs. Bronchoconstriction and eosinophil infiltration are 2 major features of asthma, and selective bronchial eosinophilia characterizes late asthmatic reactions. We compared the histologic effects of PAF-acether 6 and 24 h after its intravenous injection with those of experimental passive anaphylactic shock, which is used as a model for asthma. Six hours after PAF-acether or antigen (ovalbumin) administration, a marked lung eosinophil infiltration, particularly in the bronchial walls, was noted, together with mucous plugs containing eosinophils in the bronchial lumen. Epithelial desquamation was followed after 24 h by mucous metaplasia of the bronchial epithelium. These effects were not observed when the inactive metabolite lyso-PAF was used. Our results agree fully with the suggestion that the eosinophil mediates the pathophysiology of bronchial asthma and releases materials toxic for the respiratory epithelium. Two PAF-acether antagonists (BN 52021 and WEB 2086) prevented the eosinophil infiltration triggered by PAF-acether and by antigen. When PAF-acether or ovalbumin were injected into guinea pigs after antiplatelet serum or prostacyclin, the eosinophil infiltration was significantly reduced, suggesting that platelets or another adenylate cyclase-sensitive cell are important for the subsequent PAF-acether-induced eosinophil infiltration. Our results support an essential role for PAF-acether in an experimental model of allergic asthma.

Eosinophil Recruitment into Guinea Pig Lungs after PAF-acether and Allergen Administration: Modulation by Prostacyclin, Platelet Depletion, and Selective Antagonists

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-

Interactions between Granulocytes and Platelets with the Guinea-Pig Lung in Passive Anaphylactic Shock. Correlations with PAF-Acether-Induced Lesions

This pediatric cytological and clinical study aimed at assessing the value of nasal eosinophilia during nasal provocation tests for identifying an offending allergen. The population studied comprised 50 children aged from 4 to 18 yr; 39 of these had well-characterized allergic rhinitis, which in 21 cases was combined with asthma, and the remaining 11 had nonatopic chronic rhinitis. Nasal secretions, collected by nose blowing, were stained with May-Grunwald-Giemsa or Wright stain. The percentage of nasal eosinophils was obtained by examining the cells in the whole slides. Counts were carried out on secretions collected before challenge, after insufflation of saline solution (for verification), and 40 min after insufflation into each nostril of an allergen (housedust mite extract). The nasal provocation test was considered positive when insufflation of the allergen increased nasal eosinophilia by more than 10%, provided that the prechallenge proportion of eosinophils was less than 50%. No increase in specific bronchial resistance was noted. These results indicate that nasal provocation tests are safe, even in asthmatic children.

Nasal eosinophilia in children: its use in the nasal allergen provocation test.

Pineal uptake of two putative neurotransmitters, gamma-aminobutyric acid (GABA) and taurine, was investigated during the 24 h-cycle in mice kept in long (14L/10D) or short (10L/14D) photoperiods. Tritiated mediators were intraperitoneally injected and their concentration both in pineal gland and cerebellum were measured at several times along the nycthemere. A circadian rhythm of exogenous GABA uptake was observed in mice kept in long photoperiods: GABA uptake was high during the night, when the gland was active and low during the day. It corresponded to the pineal cycle of indoleamine synthesis. It was particularly sensitive to sudden changes of lighting. In short photoperiods, a similar cycle was observed but the result was not significant because of individual variations. Taurine uptake did not show such a circadian rhythm either in long or in short photoperiods: it was constant and rather low with large variations from one animal to another.

/pdf/variations-nycthemerales-de-l-incorporation-de-l-acide-g-3obdyf0vew.pdf

Variations nycthémérales de l'incorporation de l'acide γ-aminobutyrique (GABA) et de la taurine tritiés par l'épiphyse de la souris CD

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Eosinophil Recruitment into Guinea Pig Lungs after PAF-acether and Allergen Administration: Modulation by Prostacyclin, Platelet Depletion, and Selective Antagonists

Interactions between Granulocytes and Platelets with the Guinea-Pig Lung in Passive Anaphylactic Shock. Correlations with PAF-Acether-Induced Lesions

Nasal eosinophilia in children: its use in the nasal allergen provocation test.

Variations nycthémérales de l'incorporation de l'acide γ-aminobutyrique (GABA) et de la taurine tritiés par l'épiphyse de la souris CD