Comparative distribution of eosinophils in bone marrow, blood and peritoneal cavity in murine schistosomiasis

Eosinophilia in murine schistosomiasis is very intense and extensive, involving distinct compartments such as bone marrow, blood, peritoneal cavity and tissues. Comparison of the shapes of eosinophil concentration or distribution curves showed a synchronization of the tendencies around 50% between blood and bone marrow, 33 to 64% between bloode and peritoneal cavity, and 33 to 43% between peritoneal cavity and bone marrow. The hepatic eosinophil granulocytopoiesis or metaplasia follows the same pattern as observed in bone marrow. Schistosoma infection can be divided into three distinct phases based on the eosinophilic response: 1) non- or low-productive phase (before 35-40 days of infection), 2) acute productive phase (from 35-40 to 70-90 days), and 3) chronic productive phase (after 70-90 days of infection)

Effect of theophylline and adenosine on eosinophil function.

Eosinophils may play a critical role in asthma and bronchial hyperresponsiveness, yet the effect of theophylline on their function is not certain. We have examined the effects of theophylline on opsonized zymosan-induced superoxide anion (O2-) release from guinea pig eosinophils harvested from the peritoneal cavity and from human eosinophils obtained by differential centrifugation of blood from patients with peripheral eosinophilia. Theophylline at high concentration (10(-3) M) inhibited O2- release by 27.6 +/- 9.4% (mean +/- SEM, p less than 0.05), whereas at clinically relevant concentrations (10(-6) and 10(-5) M), it significantly potentiated this by 26.8 +/- 9.9% (p less than 0.05) and 36.9 +/- 6.3% (p less than 0.01), respectively. 8-phenyltheophylline (10(-7) to 10(-3) M), which like theophylline inhibits adenosine receptors but does not inhibit phosphodiesterase activity, produced potentiation at all concentrations. Preincubation of eosinophils with adenosine deaminase (0.1 U/ml) enhanced O2- release by 72.4 +/- 15.2% (p less than 0.01), whereas addition of adenosine (3 x 10(-8) to 10(-6) M) reversed the potentiation induced by theophylline (10(-5) M) in a concentration-dependent manner. Inhibition was greater with the A2-selective analog N-ethylcarboxamide adenosine than the A1-selective analog phenylisopropyladenosine, suggesting that A2-receptors are involved. In human eosinophils we have demonstrated a similar effect of theophylline and adenosine on O2- release. Our results indicate that therapeutic concentrations of theophylline may potentiate eosinophil activation in vivo by competing with circulating adenosine for eosinophil A2-receptors. This would be consistent with the lack of effect of theophylline on bronchial hyperresponsiveness, which may be related to eosinophilic inflammation.

Evidence for eosinophil degranulation in the pathogenesis of herpes gestationis.

Herpes gestationis is a pregnancy-related bullous dermatosis of unknown origin with associated tissue and peripheral blood eosinophilia. In this report, eosinophil degranulation in herpes gestationis was studied, and the role that the eosinophil may have as an effector cell that induces tissue damage through deposition of toxic cationic proteins is discussed. Using indirect immunofluorescence with antibody to human eosinophil granule major basic protein, major basic protein was observed both within tissue eosinophils and deposited extracellularly outside eosinophils in the dermis of eight patients with herpes gestationis. Possible mechanisms whereby eosinophils might be activated to degranulate in herpes gestationis are reviewed.

Enhanced eosinophil luminol-dependent chemiluminescence in allergic rhinitis.

Eosinophils were isolated from patients with seasonal allergic rhinitis, and their functional activity was evaluated by their luminol-dependent chemiluminescence (CL) response to opsonized zymosan and phorbol 12-myristate 13-acetate (PMA). We found that eosinophils from patients with allergic rhinitis produced a significantly greater CL response to opsonized zymosan than did normal cells. Eosinophils from both subjects with allergic rhinitis and control subjects were isolated to a purity of 95% and elicited peak values of 1,101, 901 +/- 133,708 cpm/5 X 10(5) cells (n = 7) and 417,278 +/- 25,910 cpm/5 X 10(5) cells (n = 5), respectively. The enhanced eosinophil CL to zymosan was found at times when the patients were maximally symptomatic with hay fever symptoms to ragweed pollen and again when they were asymptomatic. Eosinophils from these patients with allergic rhinitis also had enhanced CL to PMA (0.01 mcg/ml), but this increased activity was largely limited to times of hay fever symptoms. No correlation was found between enhanced eosinophil CL activity and the number of circulating eosinophils in allergic individuals. In contrast to the increased eosinophil activity, neutrophil CL to zymosan and PMA was similar in allergic and normal individuals throughout the study. These data provide evidence for the existence of enhanced oxidative metabolic function in eosinophils from patients with allergic rhinitis and raise the possibility that this particular activity is important in hay fever.

The eosinophil and the pathophysiology of asthma.

Eosinophilia of lung and blood associated with injury to the mucociliary escalator and excessive shedding of bronchial epithelium are hallmarks of both allergic and nonallergic asthma. In vitro, the eosinophil granule major basic protein (MBP) is toxic to helminths and to mammalian cells, including human respiratory epithelium. The MBP-mediated damage to the respiratory epithelium consists of desquamation and frank destruction of ciliated cells. Increased sputum MBP concentration is a good marker for asthma, and patients treated for acute asthma have high levels of MBP in their sputa, which decrease after treatment. Peak sputum MBP levels approximate concentrations toxic to respiratory epithelium in vitro. In the lungs of patients who had died of asthma, MBP has been localized outside of the eosinophil in association with damage to the epithelium. Overall, these and other findings suggest the hypothesis that the eosinophil mediates damage to the respiratory epithelium and is the prime effector cell in the pathophysiology of asthma.

Early cellular events in pulmonary fibrosis.

In this review we have surveyed recent investigations of early cellular events in pulmonary fibrosis both in animal models and in human diseases. Analysis of the interactions of the numerous cell types in the lung following injury is an almost overwhelmingly complex enterprise. In the animal models experimental design has a profound effect on results, making it difficult to compare studies when species, fibrogenic agent, dose, route of exposure, schedule of administration, time course, and analytical methods may not be equivalent. In human diseases we are rarely able to obtain data at precisely the same time point in the course of the disease even among patients in the same study, and possible confounding variables present are legion. Transcending these difficulties for the moment, can we draw any conclusions from our current knowledge of early cellular interactions in pulmonary fibrosis? What is striking is not that there are so many agents that can potentially induce pulmonary fibrosis, but that the lung has such capabilities for recovery. Although the major effector cells may all initially participate in damaging the lung and initiating fibrosis, there is evidence that they may also have the capacity to participate in subsequent repair. Macrophages may initially recruit fibroblasts and stimulate them to proliferate, only to suppress them subsequently. Macrophage production of prostaglandins can lead to suppression of macrophage, neutrophil and lymphocyte responses, thus attenuating tissue injury and the development of fibrosis. Neutrophils may initially release toxic metabolites and enzymes that damage parenchyma. However, there is evidence that they may later play a role in attenuating fibrosis, perhaps through collagenase secretion, or through as yet unknown mechanisms. Lymphocytes may initially participate in a number of damaging ways by secreting chemoattractants for other cells and participating in destructive autoimmune processes. However, there is evidence that subpopulations of T cells may dramatically shift during the course of fibrosis, leading to attenuation of the process. It may thus be useful to consider irreversible pulmonary fibrosis as the end result of a process in which the balance of normal injury/repair mechanisms is disrupted. There is clearly no single "fibrogenic event." Rather, there seem to be a number of places where disruption of balance/repair processes may begin. In diseases of unknown etiology such as sarcoidosis or IPF, loss of control may occur at the genetic level, leading to the destructive alveolitis that is the apparent precursor of fibrosis.(ABSTRACT TRUNCATED AT 400 WORDS)

Leukokinesis in bovine ostertagiasis: stimulation of leukocyte migration by Ostertagia.

A blind-well chemotaxis chamber method was used to indicate migration stimulation of bovine neutrophil and eosinophil polymorphonuclear leukocytes and macrophages as related to ostertagiasis. Live exsheathed Ostertagia ostertagi 3rd-stage larvae (L3) and soluble L3 antigen (SLA), prepared by freeze thawing and sonic disruption of L3, enhanced cellular migration for eosinophils, but not for neutrophils and macrophages. Products of lymphocytes cultured with SLA for 3 to 6 hours were also examined, using lymphocytes from peripheral blood of helminth-free cattle and cattle infected with O ostertagi or Trichostrongylus axei. Lymphokines that enhanced cellular migration of neutrophils, eosinophils, and macrophages were present in culture supernatants of SLA-stimulated lymphocytes from O ostertagi-infected cattle, but not from cattle infected with T axei or helminth-free cattle. Seemingly, L3 and SLA were stimulants of eosinophil migration. Further, neutrophil, eosinophil, and macrophage migration was modulated by lymphokines produced by SLA-stimulated lymphocytes from cattle with ostertagiasis.

Allergic complication in operated gastroduodenal ulcers: pathogeny and morphoclinical significance.

1660 gastric and duodenal ulcers were examined, of which 61 per cent showed allergic complications. The eosinophilic infiltrate associated with endarteritis and fibrinoid necrosis in the area, more accentuated than in ulcers without eosinophils is produced through a mechanism of atopic hypersensitization to food antigens. A more frequent appearance of allergic complications in the gastrointestinal tract explains why some ulcers do not heal and why certain groups of food tolerated by some patients, are rejected by others. It also imposes in some cases a desensitization treatment concomitantly with the antiulcerous one.

Dysgranulopoietic neutropenia and abnormal monocytes in childhood vitamin B12 deficiency.

Neutropenia and/or leukopenia (associated with elevated serum lysozyme levels) in three children with vitamin B12 deficiency were evaluated using soft agar culture and ultrastructural and cytochemical techniques. In two patients a marked increase in peripheral myeloid colony forming cells (CFC) was observed; whereas a marginal increase in CFC was present in the third, less symptomatic, patient. Marrow CFC was normal or slightly increased. Serum colony stimulating activity (CSA) was normal but elaboration of CSA by white blood cells was low. Normal maturation of the progenitors was present in vitro and serum inhibitors of myelopoiesis were absent. Megaloblastic neutrophils and monocytes with nuclear-cytoplasmic asynchrony were observed ultrastructurally in directly sampled marrow specimens. These cells contained autophagic and/or heterophagic vacuoles and an increase in cytoplasmic granules. Both monocytes and neutrophils also contained enlarged-disrupted centrioles. Many marrow macrophages contained phagocytic vacuoles, which enclosed disrupted neutrophils and cellular debris.

An eosinophil chemotactic factor present in blister fluids of bullous pemphigoid patients.

Tissue eosinophilia is often found in the inflammatory lesions of bullous perphigoid. A study made on naturally occurring eosinophil chemotactic activity in the blister fluids of four bullous pemphigoid patients revealed the existence of this activity in all of them. Sephadex G-25 column chromatography showed that the greater part of this eosinophil chemotactic activity was composed of low molecular substance of which the weight was close to that of vitamin B12 (m.w. 1357). The blister fluids and the sera of these patients contained elevated levels of IgE. An IgE anti-skin basement, membrane antibody was found in two if the four sera, and deposits of IgE were detected along the basement membrane zone of the involved skin in one of the patients. On the basis of these findings, we have reason to believe that an eosinophil chemotactic factor of anaphylaxis (ECF-A) participates in the accumulation of eosinophils in the lesions of bullous pemphigoid.