Human eosinophils express transforming growth factor alpha.

Abstract

SummaryTransforming growth factor a (TGF-a) is a pleuripotential cytokine with diverse biological effects, including the ability to influence the proliferation of normal cells or neoplastic epithelial cells. Eosinophils are a subset of granulocytes that normally enter the peripheral tissues, particularly those beneath gastrointestinal, respiratory, and urogenital epithelium, where they reside in close proximity to the epithelial elements . In this study, we demonstrate that the great majority of eosinophils infiltrating the interstitial tissues adjacent to two colonic adenocarcinomas and two oral squamous cell carcinomas labeled specifically by in situ hybridization with a 35S-riboprobe for human TGF-a (hTGF-a) . No other identifiable leukocytes in these lesions contained detectable hTGF-a mRNA. We also examined leukocytes purified from a patient with the idiopathic hypereosinophilic syndrome. 80% of these eosinophils, but none of the patient's neutrophils or mononuclear cells, were positive for hTGF-a mRNA by in situ hybridization, and 55% of these eosinophils were positive by immunohistochemistry with a monoclonal antibody directed against the COOH terminus of the mature hTGF-a peptide. Finally, the identification of the purified eosinophil-associated transcript as hTGF-ca was confirmed by polymerase chain reaction product restriction enzyme analysis followed by Southern blot hybridization . In contrast to eosinophils from the patient with hypereosinophilic syndrome, the peripheral blood eosinophils from only two of seven normal donors had detectable TGF-a mRNA and none ofthese eosinophils contained immunohistochemically detectable TGF-a product. Taken together, these findings establish that human eosinophils can express TGF-a, but suggest that the expression of TGF-a by eosinophils may be under microenvironmental regulation. Demonstration of TGF-a production by tissueinfiltrating eosinophils and the eosinophils in the hypereosinophilic syndrome identifies a novel mechanism by which eosinophils might contribute to physiological, immunological, and pathological responses .

Human Eosinophils Induce Mucin Production in Airway Epithelial Cells Via Epidermal Growth Factor Receptor Activation

“…Because eosinophils (15) and airway epithelial cells such as NCI-H292 cells (27) are reported to produce TGF-␣, we examined the role of TGF-␣ in eosinophilinduced mucin synthesis. First, we found that activated eosinophils release TGF-␣.…”

“…Both eosinophils (15) and airway epithelial cells (27) can produce the EGFR ligand, TGF-␣. The present studies show that activated eosinophils secrete TGF-␣ and that a product of eosinophils also increases TGF-␣ expression in the epithelium.…”

“…Eosinophils recruited to tissue express TGF-␣ in carcinomas (15) and human nasal polyps (16). Because human eosinophils isolated from peripheral blood, when activated with cytokines in vitro, produce and release TGF-␣ (17)(18)(19) in a regulated process, we hypothesized that activated eosinophils stimulate mucin synthesis in human airway epithelial cells via EGFR activation.…”

The role of the bone marrow in allergy and asthma

“…Lineagespecific cytokine effects on differentiated cells, which retain hemopoietic cytokine receptors on their surface, result in "activation" or "phenotype switching": IL-3, IL-5, and GM-CSF can activate and prevent apoptosis of basophils and eosinophils (42,59); G-CSF and GM-CSF do the same for neutrophils (60). Autocrine stimulation by eosinophils, basophils, or mast cells of their own differentiation and/or activation is thus possible, since they produce a wide range of hemopoietic and proinflammatory cytokines, including IL-3, IL-4, IL-5, IL-6, and GM-CSF (33,(61)(62)(63)(64)(65)(66)(67)(68)(69).…”

Severe airflow obstruction and eosinophilic lung disease after Stevens-Johnson syndrome

“…These diseases include asthma and the associated bronchial wall remodelling, and patients with a variety of interstitial pulmonary fibroses [16]. Indeed, there are now significant data demonstrating that eosinophils are important sources of a variety of pro-fibrogenic mediators, including: transforming growth factor (TGF)-a [17]; TGF-b [18]; vascular endothelial growth factor [19]; and type 2 cytokines, such as interleukin-13 [20]. When activated, eosinophils also release a variety of molecules that are toxic to the epithelium, including eosinophil cationic protein [21].…”