Antieosinophil serum and the kinetics of eosinophilia in Schistosomiasis mansoni.

Abstract

Although eosinophilia is a hallmark ofhelminth infections, the function ofthe eosinophil granulocyte remains unknown. The recent development of a monospecific rabbit antimouse antieosinophil serum (AES)' in our laboratories (1) has provided a unique tool by which the roles of eosinophils may be elucidated . Using a murine model of schistosomiasis, the most important helminth infection of man (2), the kinetics of eosinophilia in the peripheral blood, bone marrow, and tissue lesions was carefully established; this was followed by an examination of the effects of AES on these reactions.In previous studies of the eosinophilia in schistosomiasis in mice the animals were hyperinfected, and mortality was high in the acute stages of infection (3, 4) . Mice exposed to relatively low numbers of cercariae, however, will survive for at least a year despite the development of mild to moderate hepatosplenic disease (5, 6) . The kinetics of eosinophilia in the peripheral blood and bone marrow was studied, therefore, in mice exposed to three different intensities of infection and the responses were followed for as long as 20 wk.The effect of Schistosoma mansoni eggs on eosinophilia in the blood, bone marrow and granulomatous lesions was then examined by injecting isolated purified eggs into mice singly and multiply by various routes . While the host response was dependent on the route of injection, primary and anamnestic secondary reactions were seen after successive intravenous injections. Administration of AES under these conditions profoundly suppressed peripheral eosinophilia, induced a marked increase in eosinophil precursors in the bone marrow, and ablated eosinophils from the tissue lesions, considerably reducing their size . Materials and MethodsAnimals . Young adult female mice of the CF-1 strain (18-22 g in body weight) obtained from Carworth Farms, Inc. were used in these experiments .Eosinophilia in Naturally Infected Mice . Groups of mice were infected by the subcutaneous injection of 10, 50, or 200 cercariae of the Puerto Rican strain of S . mansoni as described by Peters and Warren (7). The worm burden in each of the experimental groups was assessed by perfusion of 10 mice 8 wk after infection (8). Eosinophil counts on five animals in each group were done weekly for the first 6 wk after infection and then at 2-wk intervals.

Eosinophilopoietin

“…The AES contained agglutinating and cytotoxic antibodies which reacted specifically with eosinophils but did not crossreact with any other formed blood elements (13,23 (1). In the present investigation, transfer to normal mice of sera or their low molecular weight fractions from animals treated with AES induced a significant increase in the eosoinophil population.…”

“…Eosinophilia is associated particularly with worm infections, allergies, and neoplasms (1)(2)(3). The increase of eosinophils in the above conditions is not usually accompanied by changes in the neutrophils or basophils, although all of the granulocytes are thought to develop from a common stem cell (4).…”

“…The antiserum had no direct effect on immature bone I Abbreviations used in this paper: AES, antieosinophil serum; ANS, antineutrophil serum; HBSS, Hanks' balanced salt solution; NRS, normal rabbit serum; MS, mouse sera. marrow eosinophils, and these cells were observed to increase in number (1,13). On the basis of these findings, we have explored the effects of AES-mediated depletion of mature eosinophils on the mechanism stimulating the prodtuction of their immatuire precursor cells.…”

“…Monospecific rabbit anti-mouse eosinophil serum (AES) was prepared as described previously (13). The antiserum was tested for specificity in vitro by agglutination and cytotoxicity assays and in vivo by its effect on the total and differential leukocyte counts in peripheral blood and bone marrow (1,13). Rabbit anti-mouse neutrophil serum (ANS) was produced in our laboratories by the method of Simpson and Ross (14).…”

“…The cell suspension was then dispersed by repeated gentle aspiration in a pipette. The total leukocyte count was determined by a Coulter counter, and the absolute eosinophil count was performed manually (1). The count obtained by the latter method represents all cell stages of the eosinophil series tlhat contain the characteristic eosinstained granules (1).…”